Cocktail Party Physics

doomsday redux

"It's the end of the world as we know it,
And I feel fine...."
       -- R.E.M.

We interrupt posting the final installment of "Brainiacs" week at the cocktail party to bring you this special announcement: the world is not going to end when CERN finally turns on the Large Hadron Collider (LHC) later this year. Seriously. I wrote about this issue way back in September 2006, and tried really hard to resist commenting further in the wake of last week's news that a lawsuit has been filed in Hawaii's U.S. District Court (Hawaii?!?) seeking a temporary restraining order against CERN and its partners in building the LHC. You are reading this because I discovered that resistance is futile. The self-styled Prophets of Doom never rest in their single-minded mission to halt scientific progress around the globe and quash the spirit of free inquiry and discovery wherever it threatens to bloom. In this case, the plaintiffs want to postpone start-up preparations for "at least" four months in order to "reassess" the collider's safety. Because, you know, it could destroy the world by creating mini-black holes, magnetic monopoles, or converting all the matter in the universe into exotic strangelets.

(*cue exasperated eye-rolling*) Oh, give me a break already. This is nothing more than the latest round of fear-mongering that always seems to accompany the start-up of a new accelerator. In fact, one of the plaintiffs is none other than "former nuclear safety officer" Walter Wagner, who spearheaded the attempt to create panic surrounding Brookhaven's Relativistic Heavy Ion Collider (RHIC) -- that lawsuit was dismissed, and rightly so. News flash to Wagner (and his ilk):  RHIC has been  operating since 2000. The world has not yet ended.  Nor did it end when Fermilab's Tevatron turned on -- not a single artificial supernova appeared, despite all the preliminary hand-wringing by fear-mongers -- or when the Stanford Linear Accelerator came online.

Perhaps some of you think I am a bit too hasty in pooh-poohing the risks associated with a big powerful machine like the LHC. Let me assure you that this is not the case: I believe very strongly that science has a responsibility to evaluate the safety of its experiments, particularly for something as massive as the LHC. LHC scientists have done so. Wagner's concerns are nothing new to anyone who has followed the development of the accelerator's design and construction over the last decade or more. The inherent risks have been fully and fairly considered by the best scientific minds in the world, who take their responsibility for ensuring safety of operation very, very seriously. To suggest otherwise is, frankly, an insult to the world high-energy physics community.

There have been two safety assessments already, and a third update has just been completed.  ("The possibility that a black hole eats up the Earth is too serious a threat to leave it as a matter of argument among crackpots," one CERN theorist told The New York Times.) We're talking about the most expert testimony any court could hope to have on record.

Why bring the courts into it at all? Because Wagner refuses to accept the scientific consensus on the issue, that's why. Apparently, he thinks he knows better than all those world-class physicists who have participated in three (to date) safety assessment reviews. Hey, he studied physics and "worked on cosmic ray research" at the University of California, Berkeley, according to Dennis Overbye's article in The New York Times, although there's no mention of Wagner earning an actual degree, apart from a doctorate in law from the the University of Northern California in Sacramento. And then he spent several years working as a radiation safety officer for the Veterans Administration. In short, he knows just enough to foster panic, and not enough to make a scientifically rigorous assessment of what the true risks are. A little learning is a dangerous thing, indeed. Pardon me for finding the "testimony" of world-class experts in particle theory more convincing than that of a retired radiation safety officer, however well-meaning.

Wagner's mysterious co-plaintiff, Luis Sancho,  might not even have that much background: he is described as an "author and researcher in time theory," living somewhere in Spain, "probably in Barcelona." Probably? If Wagner can't even locate his own co-plaintiff -- never mind give us any information about Sancho's scientific credentials -- why should we believe his statements about the LHC? Answer: we shouldn't. All the cool bloggers agree. But don't take our word for it, either. CERN has specifically addressed this issue on their Website, where you can find lay-friendly summations of the salient issues, as well as links to other relevant official documentation. There's no big conspiracy to hide the "truth," and this is not, as Wagner claims, mere "propaganda." If anything, it's Wagner who's peddling the propaganda. In fact, part of the LHC's current PR problem is that physicists are so darned honest in their assessments, they are reluctant to go on record as definitively ruling out even the most unlikely of scenarios. And that gives folks like Wagner the ammunition they need to foster unfounded panic.

Perhaps my favorite comment on the whole LHC Doomsday scenario appeared in a thread at Shakesville, where a poster identified as Astaea wrote, "Wasn't this an Angel episode? We aren't in danger till one of the scientists gets dumped by his girlfriend." Astaea is referring to a Season 2 episode of Angel entitled "Happy Anniversary," in which a brilliant physics grad student's experiment on freezing time nearly ends the world. It actually has very little to do with fears surrounding the LHC (although Sancho is apparently working on theoretical aspects of time), but I had a lot of fun analyzing the episode in a chapter of (shameless plug alert!) my book, The Physics of the Buffyverse.

In the episode, Gene (the physics student, dubbed "Time Boy" by a jealous colleague) assures a curious co-worker that his experiment isn't really about freezing time, "although that's how it would look to an outside observer." Rather, he's trying to carve out a teensy-tiny piece of space-time and remove it from reality. Anything contained within that moment would exist in its own bubble universe, forever unchanged. Time would have no meaning. He just can't get his experimental apparatus to work correctly; his math isn't quite right, apparently. I'm sure there's lots of physicists out there who could relate to Gene's dilemma. He has something they lack: a technologically advanced, fanatical demon sect intent on ridding Earth of the pesky human race once and for all. They correct his math, and when he returns to the lab and enters the new parameters, voila! A tiny drop of mercury is suspended in a timeless bubble, right there in the lab, until he turns off the machine.

Like any respectable scientist, Gene has taken safety into consideration: his experiment is equipped with various safeguards to contain the experiment, lest that tiny bubble universe escape its confines, spread, and eventually engulf the entire world. But then he overhears his girlfriend confessing her intent to break up with him after their anniversary dinner (and requisite "sympathy bone," as the girlfriend's confidante succinctly puts it).

Frankly, Gene kinda loses perspective for a bit at this depressing news. He decides to set up the experiment in his bedroom and triggers the device at the (ahem) climactic moment. Things might still have been okay, if it weren't for those meddling demons. As Gene and his (soon to be ex-) girlfriend are suspended in their private bubble, the demons remove the safeguards, and the bubble starts to spread outward, freezing everything it engulfs in its path -- until Angel managed to shut down the system in the nick of time. The bubble collapses back in on itself, and time resumes for everyone.

There's a lot to criticize in the science of this episode if one is inclined to nitpick. In some ways, it's typical "Hollywood science": a smattering of nifty-sounding physics concepts and buzzwords that, when parsed, don't seem to make much sense. In this case, you've got the notion of carving time into infinitesimal pieces --something (if memory serves) mentioned in Brian Greene's The Fabric of the Cosmos. You've got elements of tabletop plasma wakefield accelerators and laser trapping in Gene's fictional experimental apparatus. And you've got elements of relativity and black hole physics. At one point, Gene compares the effect of his temporal experiment to "a tiny event horizon."

This doesn't mean that his premise is feasible by any "real world" standard in physics. He says that if a single drop of mercury is dropped into the field created by his tabletop accelerator, and if the particles that make up the laser beams are moving at just the right velocity (the speed of light, one assumes), the mercury would be accelerated completely out of our space-time. Accelerating something to exactly the speed of light would, indeed, cause time to contract to nothing from the perspective of that object, per Special Relativity. The catch is that no object with mass can ever reach the speed of light, even tiny subatomic particles. The LHC and other accelerators can speed up particles to within 99.999% of the speed of light, but no matter how much additional power they feed into the machine, because there is a corresponding increase in mass, the particles never quite reach light speed. It would require an infinite amount of energy.

Extreme gravity -- such as that of a black hole -- might do the trick, at least, as Gene points out, from the perspective of an outside observer. Your basic black hole physics states that as an object gets closer and closer to the event horizon, someone watching its approach would see it moving more slowly the closer it gets, until it stops entirely just before crossing the event horizon, on the verge of falling in for all eternity. (From the perspective of the object itself, of course, it would continue falling into the black hole and be "spaghettified" -- Kip Thorne's colorful phrasing -- by extreme gravity along the way.) Does creating a black hole in a lab the size of Gene's seem a bit far-fetched? Sure, especially when the episode first aired. But science presses forward, and the March 2008 issue of the IEEE Spectrum magazine has a fascinating article on how scientists at the University of St. Andrews in Scotland have created an "artificial black hole" using optical fiber -- or at least something with the telltale properties of an event horizon. Maybe Gene was just really cutting edge.

The theoretical possibility of the LHC creating "mini-black-holes" is one of the Doomsday scenarios causing the current brouhaha, so this notion isn't 100% far-fetched. But here, again, there is a catch: Hawking radiation, which causes a black hole to gradually evaporate over time, proportional to its size. The bigger the black hole, the longer it takes to evaporate, and the smaller the black hole, the less time it takes to evaporate. If the LHC does, indeed, create mini-black holes -- and this is still a matter of hot debate among theorists -- they would be roughly the size of a subatomic particle and would evaporate in fractions of a second -- long before they could pose any risk to the world's continued existence. The same would hold true for Gene's temporal experiment.

I personally found it impressive that Angel's writers even attempted to build an episode around something so complicated and esoteric. They get points in my book for their cutting-edge science flair, even if everything is stitched together rather awkwardly. (A Season 4  Angel episode entitled "Supersymmetry" does a better job in this regard, cleverly drawing on the notion of string compactification in string theory as a possible mechanism for the creation of portals to other worlds in the Buffyverse -- and using all the associated jargon correctly in the process.) It's an entertaining premise, even if it's wildly unlikely. The Buffyverse is a fictional world, after all, and is therefore not necessarily constrained by the laws of physics as we understand them. It only has to be consistent with its own laws.

The same cannot be said for Wagner's contentions about the LHC. Honestly, based on what I've heard from every single physicist I've spoken with about the issues over the years, the "risks" he cites are almost as wildly unlikely as the premise of "Happy Anniversary"'s temporal physics experiment gone haywire. And Wagner doesn't have the excuse of a fictional universe to fall back on. A whole string of unlikely events  -- each with an infinitesimally small probability on its own -- would have to all come together perfectly, at just the right time, and in just the right order, to bring about the end of the world as we know it.  Wagner might as well file a lawsuit saying the LHC should be postponed until we've established that a fanatical demon sect from a parallel universe won't over-ride the accelerator's safeguards to trigger his Doomsday scenario.

survival of the fittest

On March 5, 2007, the New York Times ran an obituary marking the passing of former US senator Thomas F. Eagleton. To most post-Baby Boomers like myself, the name meant very little. But to anyone eligible to vote in the 1972 presidential election, Eagleton was the infamous Running Mate for 18 Days. Democratic candidate George McGovern picked him as his running mate, only to discover one week later that Eagleton had struggled with clinical depression, had been hospitalized three times, and subjected to electroshock therapy. They initially tried to spin it as "nervous exhaustion," but the press had a field day (plus ca change...) with the revelations, and Eagleton eventually bowed to political pressure and stepped down, at McGovern's urging, for the sake of "party unity." Fat lot of good it did, in retrospect: McGovern suffered a crushing defeat in favor of Richard Nixon. But chances are, that would have happened anyway.

Those are the political breaks: it's not an arena you want to enter if you have secret vulnerabilities, like poor Eagleton, who was, by most accounts, an honorable man despite his all-too-human foibles. We've come a long way in our attitudes towards clinical depression; it's no longer the stigma it once was, and there are far more treatment options available (albeit with unpleasant side effects accompanying the most common drug therapies). Even McGovern, the year before Eagleton died, said publicly that he regretted asking for Eagleton's resignation as his running mate: "If I had it to do over again, I'd have kept him," he said. "I didn't know anything about mental illness. Nobody did." In fact, he listed Eagleton as being among the "10 or 12 best senators" with whom he had served.

We know much more about mental illness and depression in part because of advances made in neuroscience: specifically, in the case of depression (as well as bipolar disorder, Huntington's Disease, and schizophrenia), in our understanding of the role played by a family of proteins known as neurotrophins. This was the subject of a talk here at KITP last week by Moses Chao of New York University, who focused mostly on one neurotrophin in particular: brain-derived neurotrophic factor (BDNF). There have been several studies purporting to link low BDNF levels with depression or bipolar disorder, according to Chao, and while many of those have yet to be verified, one study by Pamela Sklar  of Harvard Medical School appears to be pretty solid, and Chao's own research with lab mice genetically altered to have low BDNF levels seems to support a link as well. Apparently antidepressants help boost BDNF expression, among other effects.

To really understand why Chao and others suspect a link between BDNF levels and depression, bipolar and Huntington's, it's helpful to have a bit of background. After Chao's talk, I did what I always do when I'm intrigued by a topic: I turned to Google. Fortunately for me, there's a wealth of useful information on neurotrophins available online, and much of it is reasonably accessible to the curious non-scientist.

Nerve growth factors are secreted proteins that induce the survival of neurons. They were discovered in the 1950s by an Italian developmental biologist named Rita Levi-Montalcini. She has a compelling personal story of conducting science under siege:  after overcoming her family's objections to a woman engaging in a professional career, she graduated from med school in 1936 with highest honors and devoted herself to the study of neurology and psychiatry. But that was the same year Mussolini issued his infamous manifesto barring academic and professional careers to non-Aryan Italian citizens (notably, those of Jewish descent, like Levi-Montalcini). She fled home to Turin in 1940, as the German army was poised to invade Belgium. The family opted not to emigrate to the US, but to hide out instead. Levi-Montalcini built a small research lab in her bedroom (and, when the bombing of Turin became too intense, in the attic of the country cottage to which her family fled), where she conducted experiments on chick embryos. That, my friends, is scientific grace under extreme pressure.

Once the war ended, she returned to Turin and resumed her academic positions, moving in 1947 to St. Louis to work with Viktor Hamburger, whose research had inspired her own wartime experiments on chick embryos. She ended up staying there through retirement, dividing her time between St. Louis and Rome. In 1952, Levi-Montalcini experimentally demonstrated that when tumors from mice were transplanted to chick embryos, they induced "potent growth of the chick embryo nervous system," specifically the sensory and sympathetic nerves. But there was no direct contact between the tumor and the embryo, leading her to conclude that there had to be a nerve-growth-promoting chemical that was released to cause such a response. She was the first to successfully extract and identify nerve growth factor. And it was very potent indeed! A mere few minutes after the addition of one billionth part of a gram of NGF (per milliliter of culture medium) caused nerve fibers to grow explosively out from the ganglion. After just one day, the ganglion looked like a sun surrounded by rays (see image above). She shared the 1986 Nobel Prize in Physiology or Medicine for this work, with Stanley Cohen (who discovered epidermal growth factor).

Differentiation among cells is critical to human development, not just the brain. We all start from a single cell containing the genetic material that determines our individual characteristics. As cells divide, and divide some more, they start to differentiate -- i.e., exhibit different characteristics, play specific roles or functions, and so forth. Scientists have linked growth factor chemicals with the regulation of cell growth and differentiation. In the case of nerve growth factors like neurotrophins, they activate the process by attaching to neuron cell receptors -- molecules that act like tiny antennas, sitting on the surfaces of cells like neurons. A good analogy is the lock and key. The receptors are the lock, and can only be opened by certain protein "keys" (known as ligands), and once opened, the receptors send a series of internal signals ricocheting through the nervous system.

Neurotrophins are keys that fit the locks of specific neuronal receptors in the brain. There are four related types of neurotrophins: BDNF, nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin 4 (NT-4). Each of these correspond to a specific family of three receptors (A, B and C), known as Tyrokinase (Trk) receptors. NGF binds to TrkA; NT-3 binds to YrkC; and BDNF and NT-4 bind to Trk-B. There is a second class of receptor called p75 to which all the neurotrophins can bind, just with lower affinities. And p75 seems to play a critical role in triggering programmed cell death.

Once those "locks" have been opened, they trigger nerve growth, survival, and differentiation via a complex signaling pathway (so complex that the underlying mechanism is still not completely understood by neuroscientists). As such, they seem to play a vital role in behavior, learning and memory. BDNF acts specifically on certain neurons in the central nervous system and the peripheral nervous system (i.e., the lower spinal cord) to support the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses. It isn't just found in the brain: BDNF is also expressed in the retina, motor neurons, the kidneys, and the prostate. Stress, or exposure to the stress hormone corticosterone, has been shown to decrease the expression of BDNF in laboratory rats, and if the exposure persists, and BDNF levels continue to drop, the entire hippocampus can atrophy. Similar atrophy has been shown in people suffering from clinical depression -- hence, the suspicion that there may be a critical link between that condition and low levels of BDNF.

The process is fairly complicated in the central nervous system, where there isn't as heavy a dependency on BDNF for survival, per Chao. But in the peripheral nervous system, sympathetic sensory neurons will undergo programmed cell death (a.k.a., apoptosis) when deprived of nerve growth factor. And since there are twice as many neurons competing for a limited number of neurotrophic factors, this is the primary mechanism by which neurons self-select and differentiate. Chao's group is seeking to identify "the biochemical steps that provide specificity in nerve growth factor signaling." Thus far, we know that nerve growth factors are responsible for neuronal cell survival and death via the activation of the TrkA tyrosine kinase (for survival) and the p75 neurotrophin receptor (for programmed cell death).

Chao and his colleagues have experimentally observed the effects of low BDNF levels in the lab. First, they bred mice with a mutation in the BDNF gene to eliminate the presence of the factor entirely, but per Chao, "This proved disastrous." The mice developed normally, but died within a few weeks from cardiovascular problems, before the researchers had time to train them to engage in experimental tasks. So next, they genetically engineered the mice to have 50% less BDNF. The mice survived this time, but showed signs of elevated anxiety, learning deficits, a tendency towards obesity, and among the males, there was more aggression and hyperactivity, particularly toward other male mice. Treating those mice with Prozac, intriguingly, reversed the aggressive behavior, as did increasing the amount of exercise.

This has some interesting implications for the development and evolution of the human brain, according to Chao. BDNF levels are generally low at birth and increase dramatically in the ensuing weeks in many different parts of the brain, with the strongest expression in the forebrain and cortical regions. The prefrontal cortex develops relatively late in life, sometimes not reaching full maturity until the mid 20s -- which might explain, in part, why certain mental conditions such as schizophrenia and bipolar disorder don't fully manifest until then. There seems to be a strong correlation between increased survival and growth of neurons in the hippocampus, and higher BDNF levels. As for Huntington's Disease, this tends to develop between ages 30 and 50, with associated loss of striatal neurons -- and since these depend on BDNF for survival, lowered BDNF levels (or complete absence thereof) could be a factor in the loss of those neurons.

I was especially struck by a comment made during the Q&A by Columbia University's Stuart Firestein, another of the KITP "Brainiacs" (he specializes in olfactory receptors): "There are no switches, everything's a dial." In other words, it's not like the brain throws a switch and someone suddenly develops bipolar disorder. It's all about levels of crucial chemicals, of which BDNF seems to be one of the most critical. These chemicals are "good at the right level, bad at too low levels," and even though bipolar or schizophrenia might seem to have sudden onsets, it's more likely that levels have been falling for quite some time, and finally passed a critical threshold. Or something like that. Nobody's 100% sure. I suspect we'll have to wait for further research results before we can make a definitive call one way or the other.

What does this mean for future treatment options for those suffering from these diseases? It's a bit premature, since Chao's research is more of a fundamental variety, but certainly improving our understanding of how neurons develop (and die) in the brain, and the factors that influence their survival (or death), has important implications for the development of better drug therapies. Chao has been struggling with the challenge  of exploiting the signal transduction mechanisms of neurotrophins to treat neurodegenerative and psychiatric disorders. Apparently, even though nerve growth factors serve to protect neurons, the brain is resistant to treatments that use them. Chao attributes the failure of prior attempts to "problems with delivery and numerous side effects" in clinical trials. "Nerve growth factors are large, sticky proteins that do not diffuse very well," he said.

Chao and his colleagues have demonstrated that neurotrophin receptors in damaged motor neurons in mice, for example, can nonetheless be activated through a different, entirely unrelated receptor system (in this case, G protein-coupled receptors) through a kind of "cross-talk." Since G protein-coupled receptors are the target of many therapeutic drugs, Chao is hopeful that one day we might be able to use the "cross-talk" phenomenon to bypass the blood-brain barrier -- a major stumbling block when it comes to delivering drugs to affected areas in the brain -- without the usual side effects. However, "Ideally, we would like to treat not just the BDNF deficiency, but to be able to eliminate the mutant protein that causes those levels in the first place."

tools of the brain trade

The Brainiacs have landed at KITP! Last week was the start of a new program on the anatomy, development and evolution of the brain, which means the halls of KITP are now filled not just with particle physicists and cosmologists, but also scientists engaged in various aspects of neuroscience research. Ergo, I call them Brainiacs. That's one of the great things about the KITP: it's so very interdisciplinary in its scope, one never knows what sort of scientist one is likely to encounter on any given day, or what topics will be featured in the various scheduled talks. Today, for example, I can learn about gene networks in animal development, or mass determinations in decay chains with missing energy -- or both, if I'm feeling especially curious. Good times!

Neuroscience isn't a subject I cover much, beyond the occasional physics-based imaging technique (functional magnetic resonance imaging, anyone?). So why not have an unofficial "Brainiac Week" here at the cocktail party? We'll start with a post about the foundations of modern neuroscience. Last week I heard a talk by Winfried Denk of the Max-Planck Institute in Heidelberg, Germany, which was technically about brain circuit reconstruction using sectioning electron microscopy. My magpie mind (ooh! shiny!) got sidetracked early on, however, by the fact that most of major breakthroughs in early neuroscience came about because of the development of two critical technologies: histological staining techniques, and photomicroscopy.

We have Camillo Golgi to thank for the first one. In the late 19th century, he discovered that treating brain tissue with a silver chromate solution caused a small number of neurons to become darkly stained, revealing their detailed structure. (I've also seen the technique described as using a weak solution of silver nitrate to stain individual nerve and cell structures, in a so-called "black reaction.") Golgi's method revolutionized the field, so he can be forgiven for misinterpreting the structural organization of the central nervous system. He thought that nervous tissue was made up an intricate web of interconnected cells (the rete nervosa diffusa, or diffuse neural network), much like the human circulatory system. As scientific hypotheses go, it seemed a perfectly respectable working model, and was accepted as such by the scientific community, until a rapscallion upstart named Santiago Ramon y Cajal proffered a competing view based on his own experiments using a modified version of Golgi's staining technique.

Even today, Cajal is lauded as one of the key founders of modern neuroscience; Denk declared him the "most accomplished anatomist in neuroscience history." He was perhaps destined to turn science on its ear, since he was a notorious trouble-making hothead in his youth in Aragon, Spain. He was kicked out from numerous schools for his "poor behavior and anti-authoritarian attitude," and even landed in jail at the tender age of 11 "for destroying a town gate with a homemade cannon." I'm sure it was just a science experiment gone awry, a worthy price to pay for fostering natural inquisitiveness and scientific inquiry. (Rocket pioneer Werner von Braun got into trouble with authorities as a young boy, too, when he strapped a homemade rocket to a toy wagon and sent it speeding through the town square.)

Cajal had a sensitive, less pugnacious side as well: he was an avid painter, and very much wanted to be an artist. His father, a professor of applied anatomy in the University of Saragossa, nixed that idea, however, in favor of a more practical bent. The young Cajal was apprenticed first to a barber, then to a cobbler, before embarking on medical studies, graduating fro the medical school of Zaragoza in 1873. But he never really abandoned art: his gift for draughtsmanship would end up serving him very well in his medical and scientific career. (At right is Cajal's drawing of the neural circuitry of the rodent hippocampus, published in his Histologie du System Nerveux de l'Homme et des Vertebrates in 1911. That opus provided the foundation of modern neuroanatomy.)

His early career unfolded fairly predictably, Fresh out of med school, Cajal served as a medical officer in the Spanish Army, stationed for a year in Cuba, where he handily contracted both malaria and tuberculosis. He bounced back, though, got married, produced seven offspring, and became a professor at Valencia in 1881. A few years earlier, he used "every peseta saved from the service in Cuba" to purchase a rickety old microscope, which he used to study the structure of muscle fibers, among other things. And thus began what would become a most illustrious scientific career.

In 1887, at the age of 35, Cajal made a fateful trip to Madrid to meet with Luis Simarro Lacabra, a psychiatrist with an interest in histological research, who had himself just returned from Paris bearing brain tissue specimens stained with Golgi's method (developed some 14 years earlier). Cajal was writing a book on histological techniques, and collecting illustrations to accompany the text. Even though he'd only been studying the nervous system for about a year, he realized that the ordinary methods for studying nervous tissue were woefully inadequate. So the specimens Lacabra showed him proved to be a revelation. In his autobiography, years later, Cajal described his reactions on seeing nerve cells "coloured brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink."

The experience changed the course of Cajal's research, as he worked vigorously to apply the Golgi stain to tissues of the retina, the cerebellum and spinal cord. "As new facts appeared in my preparations, ideas boiled up and jostled each other in my mind. A fever for publication devoured me." And publish he did; his works and articles numbered more than 100 by the time he died in Madrid in 1934, not just on the fine structure of the nervous system, but also on muscles, tissues and other more general areas of pathology. (He also has an asteroid named after him -- an honor he now shares, apparently, with bloggers Bad Astronomer Phil Plait, fire-breathing atheist PZ Myers, and SkepChick Rebecca Watson. And I'll bet Cajal totally would have had a blog had the technology been available to him.)

More importantly, he arrived at very different conclusions than Golgi about the structure of the central nervous system. Recall that Golgi advocated the view that nervous tissue was a continuous web of interconnected cells. Cajal advanced the notion that the nervous system is comprised of billions of separate neurons, communicating with each other via highly specialized junctions (called "synapses" for the first time in 1897). This became known as the "neuron doctrine," which concludes that the basic units of the nervous system are individual cellular elements. Cajal also advanced the "law of dynamic polarization," concluding that nerve cells are polarized, receiving information on their dendrites and conducting information to distant locations through axons -- now a fundamental principle of neural connections.

Back then, it was a controversial view, since it contradicted Golgi's own model, but Cajal defended it fiercely, and later studies with electron microscopy bore him out by revealing that each neuron was enclosed within a plasma membrane. The two men ended up sharing the 1906 Nobel Prize in Physiology or Medicine. It seems fair. After all, Golgi invented the staining technique used by Cajal to form his hypothesis, and used it to produce the first descriptions of the different types of neurons, and the structure of glial cells, as well as the branches given off by the axon. Also, there are those in the field who argue that if you take into account the later discovery of electrical synapses, Golgi was at least partially correct that the central nervous system is a vast interconnected network -- it's just not the cells themselves that are connected.

It made for an interesting pair of Nobel lectures, though: the two men contradicted each other in their talks, each espousing his own theory of the organization of the central nervous system. For all the intensity of their scientific disagreement, the two men nonetheless respected each other's work. Writing about his Nobel honor, Cajal observed: "The other half was very justly adjudicated to the illustrious professor of Pavia, Camillo Golgi, the originator of the method with which I accomplished my most striking discoveries."

In addition to staining techniques, imaging techniques proved equally important to the development of neuroscience -- particularly the micrograph, a photo taken through a microscope to produce a magnified image of the sample. It's sometimes called a photomicrograph, and Wikipedia credits a Canadian inventor named Reginald Aubrey Fessenden with its invention, although he's best known for his pioneering breakthroughs in radio broadcast technology (as well as holding a 1926 patent for an "infuser," apparently a device for making tea). It's easy enough, in concept, to build a rudimentary photomicrograph: just attach a camera to the microscope in place of the eyepiece, place a specimen under the microscope as usual, and take as many pictures as you like.

It's a standard tool in forensics to examine trace evidence, and in biology (and neuroscience) to take magnified photos of cells and proteins -- and, if you happen to be Roman Vishniac, of insect eyes. Vishniac was a pioneer in the field, known for his photographs of living creatures in full motion, and -- more weirdly -- for taking a series of revolutionary photographs from the inside of a firefly's eye (the image at left is his daughter, Maria, seen through a firefly's 4600 tiny ommatidia). He also took pictures of the circulating blood inside a hamster's cheek pouch, and invented a method of colorization in the 1960s and early 1970s that used polarized light to penetrate cell structure in greater detail in an image.

The issue of better penetration turns out to be a critical one in modern efforts to image the brain, at least from what I gleaned from Denk's talk last week. Whereas pioneers like Cajal laid the foundations for modern neuroscience by imaging thin slices of dead brain tissue cells, researchers like Denk are coming up with inventive new ways to image living tissue -- or rather, combining lots of different optically-based techniques to see the previously "un-seeable."

For example, modern neurobiologists are combining things like multi-photon microscopy (Denk pioneered two-photon microscopy, in fact, which allows imaging of living tissue to a depth of about 1 millimeter), various types of scanning electron microscopy, fiberscopes, voltage sensitive dyes, and adaptive optics, among other tools, to engage in a kind of reverse engineering of the brain in action. The latter proved especially important because brain tissue can be tough to penetrate optically: the light scatters, and the wavefront distorts. Applying adaptive optics unscrambles the wavefront, so to speak, producing a clearer image. It's used quite a bit in astronomy to remove the effects of atmospheric distortion, compensating for any distorted wavefronts via deformable mirrors (or, less commonly, by employing materials with varying refractive properties).

Just to give you an idea of how daunting a task it can be to map out neurons and neuronal assemblies, Denk cited a seminal 1984 paper that laid out the "map" for the humble nematode (C elegans), a simple creature with a complex neurosystem model featuring 502 neurons. It took the scientists 10 years to complete the analysis, and the paper is a whopping 340 pages. It would take even longer to map out the neurosystem of a fruitfly brain, or a mouse brain, never mind the human brain.

Sure, Denk et al are using cutting-edge tools not previously possible before the advent of the modern computing age (among other advances), but ultimately, they're still doing optical imaging. Maybe that's why Denk's home page describes his work as a kind of "return of the light microscope to the front lines of biological research." By making the most of the tools available to them, and coming up with new approaches and combinations, Denk and his ilk are very much the intellectual descendants of Golgi and Cajal.

into the infrared

It's a lazy Easter Sunday, with no plans other than to lounge around the loft with the Spousal Unit and resident cat, surfing the InterTubes for amusing items -- like this wonderful site detailing fiendish experiments on Peeps -- perhaps pausing now and then to reflect on Life With a Capital "L." Among other things, I was shocked to realize that I am more than halfway through my three-month fellowship at KITP, with only four more "Journal Club" sessions to go. It's been a lot of fun: we've had sessions on "The Art of the Book Deal"; a rousing panel discussion on ongoing tensions between scientists and the media (which the Spousal Unit describes at length here); a brainstorming session on scientists in Hollywood, in which we devised the framework for a physics-centric (or at least science-centric) TV series; and of course, a session on Science Blogging 101, in which I set up a blog for our cat, Clio, on Blogger just to illustrate how easy it is. (If Chad at Uncertain Principles can write a book about conversations with his dog about quantum mechanics, Clio can have her own blog.)

My musings reminded me that I've been meaning to write a post about the infrared photography of Caltech's Tom Prince, who's currently at KITP on sabbatical before heading back to Pasadena to take the helm of the newly funded Keck Institute for Space Studies. We hope it will be abbreviated KISS, making it possibly the best science acronym ever. As a handful of shyer souls beat a hasty exit when I asked if anyone wanted to participate in a practice press conference, Tom graciously volunteered to be the guinea pig during the session on Press Conference Protocol. (I have since learned to give people advance notice and ferret out volunteers beforehand.) He spoke for 10 minutes or so about his hobby -- complete with sample photographs of KITP in the infrared -- and took a few questions from the audience afterward. The photographs are truly stunning. Check this out:

And here's another that captures the nearby beach and big blue sky:

It's tough to pinpoint at first what makes these photographs so striking, but it's related to the properties of near-infrared light -- i.e., light just beyond the visible spectrum (wavelengths between 700 nm to 1200 nm, usually falling around 900 nm). Infrared photography records what the human eye cannot see. Many materials reflect and transmit IR light in a different manner than visible light. So there are elements in IR images that resemble photographic negatives (although these pix are clearly not negatives). Blues, browns and dark greens in shadow appear dark, while reds, whites and greens in sunlight appear light. Take a portrait of your loved one and the skin will have a chalky appearance in the IR image, red lips will be pale, and the eyes will show up as dark spots. Vegetation comes out very bright in IR photographs, while a clear sky appears dark, apart from the occasional white cloud.

Andrew Davidhazy of the Imaging and Photographic Technology Department at the Rochester Institute of Technology explains on his Website that this last effect occurs because of "the high near-infrared transmission characteristics of green chlorophyll and high infrared reflectance of the underlying cellulosic structure of these subjects." Among other things, this can be used in aerial surveys and reconnaissance to distinguish trees and grass from diseased or dead trees or burned grass, since those appear dark in IR photographs. (You do need to use a special filter for IR photography, and special IR film if you're using a traditional camera, since otherwise the infrared effect is masked by the exposure to visible light. And  note that this is not the same thing as thermal imaging: IR photography uses radiation reflected from the subject to form images, whereas thermography uses IR radiation naturally emitted by objects, and requires special IR sensors.)

Ideally, the photographer takes all these effects into consideration when composing a scene or choosing topics. Tom said that he tries to take his photographs on bright sunny days -- very common in Santa Barbara -- because there is more IR light when the sun is bright, making the high-contrast effects that much stronger, although he's gotten some interesting, moodier effects in photographs taken on cloudy days. Other suggestions from IR photographers include taking pictures in a graveyard, because the grass will come out almost completely white, with the dark tombstone seeming to almost float eerily in space. Stone buildings covered in ivy or other creeping vegetation also yield striking, high-contrast IR images. And apparently, if you photograph people wearing sunglasses, it's sometimes possible to see the eyes behind the opaque shades in an IR photograph, because the filters used in the sunglasses don't have any effect on IR light.

Tom is just one among thousands of IR photography enthusiasts around the world, as I discovered when I Googled the term after his talk. My research yielded a rich lode of fascinating details. I already knew that infrared light was discovered by Sir Frederick William Herschel, best known for building killer telescopes in the 18th century and discovering the planet Uranus. In 1800, Herschel took some time away from his telescopic observations to fiddle with a different kind of experiment: passing sunlight through different colored filters. The different colors seemed to pass different amounts of heat, so he took things one step further, and passed sunlight through a glass prism to create the telltale rainbow spectrum of visible light. Then he measured the temperature of each bulb.

Herschel found that not only were all the measured temperatures higher than the controls, but those temperatures increased with each color from the violet to the red part of the spectrum. And when he decided, just for curiosity's sake, to measure the temperature just beyond the red portion of the visible spectrum, it had the highest temperature of all. Herschel attributed the effect to "calorific rays," and subsequent experiments demonstrated that they behaved just like visible light -- not surprising, since what he'd discovered was infrared radiation. It was the first demonstration that there were types of light beyond the visible spectrum.

Infrared radiation spawned not only a host of practical applications, but also an entire field of astronomy. Infrared telescopes can see past the huge amounts of interstellar dust in the cosmos into the very hearts of galaxies. People had figured out how to take infrared photographs as recently as the 19th century, but it wasn't easy. In the early 20th century, however, scientists developed special infrared dye sensitizers to create infrared films, and the use quickly spread from the laboratory into more practical applications. In the late 1920s, for instance, John Logie Baird developed the first working infrared videosystem, Noctovision, which, among other things, made it possible to film nighttime scenes during the day (a technique known as "day for night," or, as Jen-Luc Piquant prefers to phrase it, La Nuit Americaine). Just underexpose the shot a little bit; then a dark sky with bright moon-lit clouds and deep shadows looks pretty much how we'd expect a nighttime scene to appear.

Today, IR photography has found application in the study of plant diseases, revealing changes in pigment or cellular material; in paleobotany; to enhance details of deeply pigmented tissues in photomicrography in the biological sciences; and by the textile industry to detect irregularities in fibers. It is also used quite often in criminal investigations to examine and identify cloth, fibers and hair, and it's become a standard laboratory tool for imaging faded, damaged or altered documents. It makes clear the differentiation between pigments, dyes and inks, so if something has been overwritten, you can sometimes figure out the underlying text using IR imaging techniques. This proved handy in the 1930s, for example, when people wanted to see what lay underneath the blacked-out portions of documents vetted through censors.

Davidhazy has a terrific example of this infrared luminescence (or fluorescence in the infrared) on his Website. Twenty years earlier, a mother had placed a letter to her children in a homemade time capsule and buried it near the cornerstone of their house, intending it to be unearthed and read 20 years into the future. Unfortunately, when he now-grown children did so, much of the ink had washed away because water had seeped into the box. There was residual ink, however, albeit not visible to the human eye. When the letter was illminated with light devoid of IR wavelengths, the residual inks fluoresced in the infrared, and when filtered through an IR transmitting filter placed over the lens of a camera, those emissions were captured on Kodak high-speed infrared film. And the children were able to read their mother's words after all.

The rise of the digital camera is beginning to eclipse the use of actual IR film and traditional cameras. No longer is there any need to fuss with all those chemical and mechanical processes. Instead of focusing reflected incoming light onto a piece of film, a digital camera focuses that light onto a semiconductor device -- either a charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS) technology -- that records light electronically, converting that light into electrical charges.

The CCD and CMOS chips used in digital cameras are already very sensitive to near infrared, not just visible light, which is why these cameras come equipped with filters to remove the infrared. Tom Prince simply adapted his standard digital camera with an opaque filter that cuts out the visible light and enhances the infrared, for a cost of roughly $250. (He doesn't recommend doing so yourself unless you have easy access to a clean room, as it requires opening the camera and exposing the delicate electronic innards to particles in the environment.) Using such a filter, you can't see the shot through the viewfinder. Tom (and, I assume, other IR photographers) have to compose the shot with the filter off, steady the camera in place, put the filter back on, adjust the focus, and then take the shot. It's a little hit and miss, but as the images featured in this post attest, you can get some genuine stunners.

So what happens when you take a color photograph using an infrared filter? Tom has tried that, too, and it is possible to do so. It's just a bit more work, since you need to take two pictures: one with the IR filter, and immediately after, another regular photograph. They need to be in alignment, too, so most IR hobbyists recommend using a sturdy tripod to hold the camera in place. And don't forget to take both photos with the same aperture settings to ensure consistent depth of field. The two photos can then be merged in Photoshop, where one can modify the color channels directly. Any color image can be broken down into the red, green, and blue channels (which is how color images are created); IR light in that context is just another "channel." Here's one of Tom's color IR photographs:

The overall effect isn't quite so much of an eerie contrast, although one still gets the sense of something being "different" about the photograph. Here's the same scene in standard IR black-and-white, for comparison:

You can see many other examples of infrared photography by several different photographers by browsing this gallery of links, and several examples comparing and contrasting color and B&W IR photographs here. Why not browse a little bit and savor a novel way of looking at the world? It's way cooler than rose-colored glasses.

virulent ramblings

Since we're all in mourning this week for the loss of Arthur C. Clarke, I thought I'd put in a good word for one of my other favorite sci-fi authors: Connie Willis. There are many reasons I love Willis' work, not least of which is her ability to mix funky, cutting-edge science (time travel, chaos theory, neuroscience) with literary and historical references (Lincoln's Dreams), witty dialogue (Bellwether), colorful characters, elements of farce and slapstick (To Say Nothing of the Dog), and somehow also manage to break your heart (Passages) -- usually all in the same book.

Her big breakthrough novel was the Hugo-Award-winning The Doomsday Book, in which a young idealistic medieval historian in futuristic Oxford, England, travels back in time to the Middle Ages and finds herself trapped in a small village just as the Black Plague reaches the area. Spoiler alert! Everybody dies. Duh. Every sci-fi fan knows about the "Grandfather paradox," and savvy writers like Willis tend to adhere to the trope that time travelers can't change the course of history. And it's a matter of historical record that most villages saw 80%-100% mortality rates. Most of the European population was wiped out during the Plague Years. The fact that people panicked and fled only helped spread the disease faster.

Panic reactions and the spread of global disease was actually the subject of a session at the recent APS March meeting in New Orleans by researchers from the Max Planck Institute for Dynamics and Self-Organization. Recognizing that human beings will "change their dispersal characteristics" in response to local infections -- i.e., panic and flee to avoid becoming infected themselves. Not surprisingly (to me, anyway), they found that "the individual rationale of avoiding an epidemic wave... actually facilitates epidemic spread" -- at least in one of their models. A more fully developed dynamical model apparently showed the same effect, but also "an increased extinction probability of the epidemic as a function of increasing dispersal response." In other words, sure, the hypothetical "epidemic" spread faster as individuals dispersed broadly to avoid infection, but this also increased the likelihood that the epidemic would die out -- hopefully before everybody fell victim to the disease.

Epidemiological models of the dynamics of epidemics are tough nuts to crack precisely because there are so many unpredictable variables: not just irrational (or even rational) human behavior, but the behavior of whatever is the cause of the disease itself, whether it be a bacteria or a virus (or a virus that targets bacteria), whether it's vector-borne, or otherwise disseminated. Viruses can mutate into many different strains, for starters, and in some of these multistrain cases -- dengue fever, the Ebola virus --  the antibodies produced by the human immune system to ward off the primary infection can actually increase one's vulnerability to acquiring a secondary infection with a different strain.

So naturally, scientists would like to have a clearer picture of human mobility patterns -- preferably one that can be universally applied. There's good news on that front! Researchers at Northeastern University and Notre Dame University have analyzed cell phone usage to demonstrate that human mobility can be described by the same universal pattern, regardless of what our individual travel habits may be. It's been tough to model this sort of thing in the past, because scientists just haven't had the tools required to monitor the movements of a large number of people in real time. The ubiquitousness of the cell phone in modern society has changed all that: now it's possible to track people's movements by following the cell phone trail.

These patterns could be useful in urban planning, traffic forecasting, and of course, the spread of diseases and viruses. The latter would include the possibility of cell phone software viruses, in which malevolent code could be transmitted either via text messaging or through Bluetooth connections between devices. Each transmission pathway would require different countermeasures, according to Pu Wang of Northeastern (one of the speakers at a March Meeting session), since text message viruses, like email, would spread through social networks rather than the physical location of the actual cell phones, whereas a Bluetooth-specific virus would spread among cell phones in close proximity.

Some primer notes: The technical definition of a virus is "a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell." (I'm sure there's a more complicated definition than that, because otherwise, most reproductive processes would fall into this category.) They cause everything from the common cold, to rabies, yellow fever, smallpox, and the flu, and they don't respond to antibiotics, although some antiviral drugs have been successfully developed to treat a few critical types of infection, and vaccines can also prevent infection in the first place (polio has almost been eradicated, although rare cases still pop up now and then).

There are various historical records dating back to the 10th century indicating that folks understood something about the infectious nature of smallpox and measles, but I was intrigued to learn that a physician named Ibn Khatima discovered in the 14th century that the bubonic plague (Black Death) and other infectious diseases were caused by micro-organisms entering the human body. And of course, by the late 18th century, Edward Jenner had figured out that a milkmaid who had caught cowpox proved immune to smallpox (a related virus), and used it to develop the first smallpox vaccine. (Smallpox has been eradicated, per the pronouncement of the World Health Organization in 1979.)

There are countless strains of any one virus, and different types of viruses beyond that, which makes one wish there existed something like a periodic table of viruses just to keep everything straight. But we did learn the difference between simple viruses like the cowpea chlorotic mottle virus (CCMV), and bacterial viruses (those that attack bacteria): CCMV has a more easily compressed single-stranded RNA center, while bacterial viruses contain double-stranded DNA. That's noteworthy because a DNA strand typically measures some 17 microns in length, whereas a viral protein capsid is 60 nanometers -- 1000 times smaller than the length of the DNA. So the DNA has to fold up and squeeze into a very tiny space. That means the bacterial virus's capsid must be strong enough to contain the immense internal pressure of roughly 50 atmospheres. (Yowza!) Another difference is that unlike CCMV, bacterial viruses bind to receptor points on bacteria, and then the DNA comes shooting out, just like the cork of a just-opened bottle of champagne.

Bogdan Dragnea of Indiana University in Bloomington is one of a growing number of researchers interested in the physics of viral protein cages, or capsids. They're intriguing because they self-assemble to contain nucleic acid (RNA or DNA), and Dragnea is among those toying with constructing artificial viruses containing nanoparticles, droplets, drugs, or other elements besides nucleic acids. Among other things, he's embedded negatively charged gold nanoparticles inside viral capsids by exploiting their attraction to the positively charged proteins lining the capsids. This mimics the interaction between "anionic genetic contents" (RNA and DNA) and those same positively charged proteins in real viruses.

He's also encased fluorescent quantum dots of cadmium selenide crystals in a shell of zinc sulfide, which he then used to track how long it took for a particular virus to travel across a cell membrane (because the dots glow for extended periods). Dragnea's artificial viruses aren't "infectious" the way a natural virus might be, but he does believe it may one day be possible to replace vaccines -- made from actual viruses -- with completely artificial versions, thereby avoiding the risk of causing an outbreak of the very disease one is trying to prevent.

It's all part and parcel of an exciting new field called physical virology, which is getting its very first Gordon Conference next February (Dragnea is one of the organizers). Dragnea's early work focused on the Brome mosaic virus. The March Meeting session featured new research using CCMV which specifically infects the cowpea plant, more commonly known as the black-eyed pea.  Just imagine the poor little cowpea, innocently hanging out in a field, photosynthesizing to its heart's content, only to fall victim to a tiny invader that causes yellow spots to form on the cowpea's pretty leaves. It's unsightly, and and ultimately fatal to the plant. Next time there's a shortage of black-eyed peas, blame CCMV.

CCMV is a favorite choice for physical virologists because it's so easy to replicate and use -- it's like the hydrogen atom of viruses. That's because it's so evolutionarily designed for self-assembly that, according to UCLA's Charles Knobler, you can literally break them into their constituent parts, put them into a test tube with some sort of solution, shake them up a bit, and get fresh virus out. Under the right conditions, its purified coat protein mixed together in vitro with its genetic material will spontaneously assemble into infectious particles.

Wow. That's like the T-1000 in Terminator 2: Judgment Day literally reassembling itself after being frozen solid with liquid nitrogen, blown into tiny bits, then having the bits melt back into liquid form and "find" each other. The cowpea population could be doomed. (Jen-Luc Piquant isn't that fond of black-eyed peas anyway, but the plant leaves are so pretty.)

Knobler is investigating what determines the size of a virus. The answer appears to be some combination of polymer length, molecular weight, and capsid size, in an intricate self-assembling interplay. It is possible to manipulate the length of protein building blocks in the CCMV and the size of the capsid in such a way as to use virus proteins not only to make nonbiological particles that contain foreign molecules, but also that conform to a specific intended structure.

Building on the spontaneous re-assembly that occurs when purified viral RNA and capsid proteins are mixed in a solution at just the right pH and ionic strength, Knobler tweaked the parameters a bit, changing the solution conditions to cause the formation of empty capsids, multishell structures, tubes and sheets. He also examined the self-assembly process with different molecular weights, and noted that two distinct capsid sizes seemed to be preferred: 22 nanometers for lower molecular weights, and 27 nanometers at higher molecular weights. (I'm admittedly a bit fuzzy on the significance of that, but it's nice to have things narrowed down so specifically.)

Adam Zlotnick and his colleagues at the University of Oklahoma Health Sciences Center can manipulate the CCMV coat protein in such a way as to redirect its self-assembly to produce tubular structures. They didn't rely simply on static models based solely on the structure of the CCMV virus, which Zlotnick believes can lead to false predictions, namely, that CCMV capsids are extremely stable, and the assembly relies critically on hexamer (6 linked molecules) formation. That turns out not to be the case. "Experimentally, we have found that capsids are based on a network of extremely weak pairwise interactions and that pentamer (five linked molecules) formation is the critical step in assembly kinetics," he said. Far from being static structures, viruses are "very dynamic molecule machines based on weak energy interactions."

Furthermore, because those interactions are weak, it is possible to interrupt the assembly process to generate, say, tubular structures in addition to spheres -- or even keep the virus from forming completely in the first place. (Low pH seems to be one way to do the trick.) His kinetic models more closely match those experimental observations. And the fact that it's possible to disrupt and manipulate the process bodes well for the bottom-up production of manmade nanostructures via self-assembly for any number of applications, including the development of new antiviral drugs.

Per Zlotnick: "Knowing the structure of a virus gives us a snapshot, but add the knowledge about the kinetic process of assembly, and we have a much more complete picture" of how a virus works. And the more we know, the more we can manipulate and control. Perhaps one day, we could even defeat the common cold. But let's start with the saving the humble cowpea.

Sir Arthur C. Clarke, 1917-2008

"Sometimes I think we're alone in the universe, and sometimes I think we're not. In either case the idea is quite staggering." -Sir Arthur C. Clarke

Arthur C. Clarke, one of the Golden Age science fiction writers who fired the imagination of would-be space explorers everywhere, died today in his home in Sri Lanka. Clarke's 2001: A Space Odyssey was probably one of the most influential novels in the genre, along with the Stanley Kubrick movie made from it. His creation Hal  was an early model (good and bad) for AI constructs, along with Asimov's Three Laws of Robotics. From his first novel, Prelude to Space, which foreshadowed the Apollo missions to the moon, to The Fountains of Paradise, in which he described the construction of a space elevator now in the planning stages, Clarke, an engineer, was a practical visionary whose predictions had a habit of coming true. In 1945, he sketched out in a published paper the utility of geosynchronous satellites for communications purposes almost ten years before the folks at Bell Labs launched the Telstar and Echo satellites. Though he was by no means the originator of the idea, he was certainly a popularizer and active proponent of it, as he was of technology in general, and space exploration in particular.

Though his characters could be two-dimensional, his science was generally impeccable and inspiring. No one in my childhood reading made space or the possibility of "slip[ping] the surly bonds of earth" seem so real to me, not even Star Trek. It was Clarke who taught me what geosynchronous orbit and LaGrange points are, proving that a spoonful of fiction helps the mathematics go down, at least to people like me. That inspiration wasn't confined to interesting kids in science fiction. “I’m rather proud of the fact that I know several astronauts who became astronauts through reading my books,” Clarke once said. I can only imagine how many engineers and other space scientists he inspired.

Aside from his novels, Clarke was best known for his three laws of science and technology:

1. "When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong."
2. "The only way of discovering the limits of the possible is to venture a little way past them into the impossible."
3. "Any sufficiently advanced technology is indistinguishable from magic."

While the first two are important for egging on inventions and new discoveries, it will be useful to remember the third law should we ever meet an intelligent extraterrestrial civilization face to face, since far too many of us are prone to worship what we don't understand, as Clarke also illustrated in his Rama books. Generally dismissive of religion, Clarke was still painfully aware of the necessity of some kind of guiding morality. "As our own species is in the process of proving, one cannot have superior science and inferior morals. The combination is unstable and self-destroying," Clarke said in 1967. It's still a timely message.

Thanks for years and volumes of inspiration and great Saturday afternoons. RIP.

[Don't blame Jennifer for this. It's one of Lee Kottner's insidiuos posts, cross-posted from Spawn of Blogorrhea with Jennifer's consent.]

cut and run

Is anyone else tempted to take all their money out of their respective bank accounts and IRAs and just hide everything under the mattress, so we'll have ready cash after the apocalypse? That's how I'm feeling at the moment, after watching one of the nation's most venerable financial institutions, Bear Stearns, crash and burn in the space of just a few days. A few weeks ago, their shares were valued at around $170. By last week, that had dropped to $70. And this morning, I awoke to read that, thanks to a bailout by the feds, J.P. Morgan will be buying Bear Stearns for the rock-bottom price of $2 a share. The entire Bear Stearns headquarters building in Manhattan is worth more than that! Maybe they'll throw in a set of Ginzu knives with the purchase. ("Now how much would you pay?")

How art the mighty fallen. It wasn't that long ago that Bear Stearns was listed as one of the most admired financial institutions. Turns it out it was all an elaborate house of cards, much like the Enron meltdown of a few years ago, except this time it's worse, because stocks are tumbling globally, not just in the US. That's what happens when a company (or a nation) over-extends itself and takes on far too much debt. I'm sure James Cayne, the former CEO, feels just terrible -- maybe even badly enough to pause for reflection while rolling in the great wads of cash he raked in during his tenure: $232 million in compensation from 1993 to 2006. Personally, I think he should be forced to give some of it back to help bail out the company he helped drive into the ground. Call it a return to the traditional conservative values of accepting responsibility for financial imprudence.

No doubt Bush and Cronies will dismiss this as one of those statistical outliers, a "rare event" in the financial markets, instead of something that could have been avoided had management been a bit more prudent. I find myself wondering what Eugene Stanley of Boston University would have to say about the mess. He's one of the pioneers of econophysics, and was on hand at the APS March Meeting in New Orleans to talk about his latest research: namely, that these so-called "outlier" rare events actually occur in regular patterns, and thus should be incorporated into economic theories, which to date have dismissed them as "anomalies."

Stanley can make this statement with some degree of confidence because he's just completed analysis (with the help of numerous grad students and post docs) of an enormous amount of financial data -- 200 million transactions on the New York Stock Exchange spanning a two-year period. That's far more than has ever been included in such analyses before (10<8> data points, compared to 10<4> data points). "Classic economic theories not only fail for a few outliers, but there occur similar outliers of every possible size," he said. "So ignoring them is not a responsible option." He's applying the tools of physics to figure out if there are underlying unifying principles (equivalent to physical "laws") that dominate the NYSE and other financial bodies and institutions -- i.e., whether there is "an identical set of laws hat hold across diverse markets, and over diverse time periods."

Econophysics is a relatively new field, emerging in the mid-1990s thanks to the work of several physicists who decided to apply the tools of statistical mechanics to the complex problems posed by financial markets in particular. It was the right time for this to happen: not only did huge amounts of data suddenly become available in the 1980s, but there were an increasing number of PhD physicists fleeing the stagnant job markets in their fields for Wall Street, finding work as "quants" -- basically, sophisticated financial analysts. At the same time, according to Wikipedia, "It became apparent that traditional methods of analysis were insufficient. Standard economic methods dealt with homogenous agents and equilibrium, while many of the more interesting phenomena in financial markets fundamentally depended on heterogenous agents and far-from-equilibrium situations."

Lots of different physics models have been applied to financial systems, including percolation models, diffusion theory (the famed Black-Scholes equation garnered a Nobel Prize in Economics), models with self-organizing criticality of complexity, models developed for earthquake prediction, even chaotic models originally developed to study cardiac arrest. That was the topic of another paper at the March Meeting, in fact. Nothing that fractal analyses of cardiac rhythms suggest that healthy people have complex cardiac behavior -- compared to the rhythms of unhealthy people, which are more random or periodic in behavior -- researchers at Brigham Young University are looking into whether similar complexity might be an indication of a healthy company. The title of their p