Tuesday, February 27, 2007

Book review: The Physics of The Buffyverse



The Physics of the Buffyverse might just yet be the most unlikely title (or subject material) for a popular science book. I mean, Buffyverse? That fictional universe where Buffy the vampire slayer and her gang of Scoobies run amok destroying vampires and other such bizarre beasties (or is it the other way around)? The physics of Buffyverse? Using that most unlikely material as her inspiration, Jennifer Ouellette decides to write a book about some of the most interesting and important concepts in science.

The Buffyverse is undeniably a crazy place. Of course, given that you can find almost anything in California, if a fictional Sunnydale had to exist, it would be in Southern California. And here is where the Hellmouth is located, connecting the world with another dimension, filled with vampires, witches and a host of other unworldly creatures. So, where does science fit into all this gobbledygook? It’s hard to imagine, but Ouellette uses episodes, events and characters from Buffy to explain science concepts, and the science in the Buffyverse itself.

My impressions of a book are not always totally unbiased. If the book starts well, I almost always will finish reading it. If it doesn’t start well, even if the book starts to become fascinating, I invariably have a poorer opinion of it. In this case, the first chapter of the book is fantastic (and of course, I finished the book). Ouellette starts to describe the various types of demons in the Buffyverse, and surprisingly (but very convincingly) draws parallels from the natural world. While describing Dracula (or a creature who thought he was Dracula) Ouuellette draws out historical fables that described the evolution of the modern day Dracula, and then goes on to describe how some of the aspects of vampire lore that actually resemble real diseases or phenomena. For example, there is a hereditary disease called porphyria, where the body doesn’t have enough heme (which is an iron-rich pigment in the blood, essential for binding and transporting oxygen). In certain types of porphyria, patients are super-sensitive to light. It perhaps was also true that porphyria patients were given fresh blood as a remedy (though it doesn’t work). Could this have been a starting point for the legend of the vampire or werewolf? The first chapter builds on from this, and delves into other creatures of the Buffyverse, and how sometimes they draw parallels from real animals or plants or insects, and how (even more frequently) they violate the laws of physics or chemistry.

Surprisingly, some of these parallels work, and Ouellette does write with a simple, engaging style that avoids too much scientific jargon. From this starting point, Ouellette starts to draw from more Buffy material. There’s plenty of magic in Buffy, and that almost invariably means plenty of flashes of lightning, or sparks emanating from some demon’s hands, or someone disappearing in a flash (followed with some smoke). These provide excellent examples from which to build on the concepts of electromagnetism, conduction, the atom, or thermodynamics. However, it sometimes becomes a stretch when Ouellette starts to reason out plausible explanations for magic.

As the book goes on, and starts delving into more complex aspects of Physics, the subject matter sometimes seems to hold back the book, and the explanations of concepts. It becomes harder to accept the analogies that Ouellette makes from Buffy, as she starts to explain wormholes (“shortcuts through space and time”), or string theory, or even the improbability of time warps. But to Ouellette’s credit, after every section that seems to be too much of a stretch, she comes up with very imaginative ways to illustrate some of physics’ most complex concepts using Buffy examples. I had to smile while reading the section on Schrodinger’s “cat in the box”problem. Here Ouellette reminds us about Miss Kitty, Willow’s adopted kitten. The kitten appears on a couple of shows, and then mysteriously disappears, and there’s some vague explanation of a cross-bow accident, but no clear story. So, is Miss Kitty dead or alive? Ouellette imagines a room where Miss Kitty is in a corner, in front of a loaded crossbow, which is triggered by a Geiger counter, and there is no one in the room. For the Geiger counter to click, a radioactive uranium atom must decay, but has a 50% chance of decaying. If it decays, the crossbow will fire, and kill the kitten. If not, the kitten would be alive. Logically, the kitten cannot be both alive and dead. But to find out if it is alive or not, we need to enter the room and see. What is the state of the kitten before we enter? Now this, I thought, was an extremely imaginative way to describe the “cat problem” AND use an episode from Buffy to explain it!

Still, it is difficult to be constantly intrigued by Buffy craziness. Unfortunately for Ouellette, her choice of subject material, Buffy, holds back the book (and this is purely my own opinion). Buffy, though a cult-classic, is not that kind of cult-classic. It is not Star Trek. Most Trekkies are dedicated science buffs, and a whole bunch of scientists are devoted Trekkies. They love to watch, and re-watch endless episodes of Star Trek, and analyze where the science was incorrect or highly improbable (teleportation, or even “warp speed”), or where it was plausible (a silicon based universe), or where the creators got it just right. Unfortunately, the biggest fans of Buffy aren’t science geeks. It falls squarely in the realm of fantasy which is mostly improbable or absurdly impossible (which Ouellette gets, of course, and uses often in her book). Some of us science buffs devotedly watched Buffy purely for the ravishing Sarah Michelle Geller, some great action sequences, and little else. Many of the science concepts explained in the book, while well written, may not appeal to a hard-core science buff (though I mostly enjoyed it). There is a lack of detail on many topics (which is understandable in a popular science book). This is where the power of a footnote could come in. With footnotes, authors can often explain details of scientific concepts that need more explanation (for the serious science buff), but which allow a less interested reader to ignore. Some footnotes (with the equations behind the science, or more information) would have gone a long way in adding substance to the book. On the other hand, devoted fans of Buffy may not spend sleepless nights worrying about how a vampire could not reflect off a mirror (if we can see them, they must reflect light. If they reflect light, they will reflect off a mirror), but can be knocked out by a baseball bat or bump into furniture. I’ve known a few dedicated Buffy fans, and none of them cared for the science behind it.

Any technology far more advanced than our own present technology or science will appear as magic. This was something the creators of Star Trek realized, and so (like a lot of Sci-fi) by placing themselves in the future made their own gadgets more plausible. However, the Buffyverse is all magic. It does not try to, or pretend to, have rational explanations for anything. Sometimes it goes out of the way to make something impossibly unscientific. Therein is the problem. One cannot always successfully explain science by basing your explanation on the absurd.

So, Ouellette certainly has written an excellent book to bring together her two great loves (Buffy and Physics, incase you were still wondering), but that may not be what we all crave. Still, I certainly did enjoy the book in parts. It is not a book that I could read for long hours at a stretch (something I usually do with most books), as it got a little repetitive, and sometimes was too simplistic. But it did work very well when read in small bits over many days. It is a welcome addition to the growing list of accessible popular science books that deal with detailed science. But it is not a science book I’d keep going back to.

Friday, February 23, 2007

Smell food, die early

An area of science I’ve long been fascinated by is calorific restriction (eating less) resulting in huge increases in lifespan (here are two older posts I’ve written about this topic). But the field is growing in complexity, and has gone beyond just the SIR2 gene that extends lifespan in starving organisms.

The fact that eating less leads to longer lifespan has been well proven. But it would seem radical to imagine that our other senses, particularly our sense of smell could perhaps alter that. Researchers have now found otherwise, and perhaps the smell of food could influence how long we live.

Cynthia Kenyon’s lab first connected smell with increased survival on starvation diets. Initially, they did their study on worms, called C. elegans. Worms, like almost all other organisms (including mammals) live 20- 50% longer than average (when on a normal diet), when they were placed on calorifically restricted diets. These researchers observed that if they destroyed (literally fried) the olfactory system of worms with a laser, the worms also lived longer than normal and resembled worms that were on calorifically restricted diets. This made other researchers wonder if smell and calorific restriction resulted in similar effects.

In very recent studies, researchers worked on fruit flies, the ever popular Drosophila melanogaster. Flies too are known to live up to 50% longer when on very low calorie diets. These researchers found that when flies on dietary restriction (which usually live longer than average) were exposed to “tasty” odors (yeast smells, which are clearly yummy to flies); they no longer lived long, but died at near normal, average ages. However, the lifespan of flies on a normal diet did not change when these flies were exposed to these odors. This suggested that just the smell of food could reverse the effect of calorific restriction.

So now, to rigorously prove this theory, these researchers found mutant flies where a specific odorant receptor, which enables these flies to smell, was non-functional. Fantastically, when these flies were kept on a restricted diet (where they should live long), and were now exposed to the yummy food odors, they still continued to have an extended lifespan. What was even more convincing was that when these researchers restored this odorant receptor (by putting back a functional gene into the flies), they could now detect yeast odors, and so died earlier even when on a calorifically restricted diet. In the authors’ own words:

Olfactory-receptor function constrains the beneficial effects of dietary restriction, indicating that consumption is not the only way that nutrient availability modulates longevity.

Of course, this study hasn’t yet been proven in mammals, while calorific restriction has been well proven in many mammals, from mice to monkeys. Still, given that it works in evolutionarily diverse organisms like flies and worms, there is a good likelihood that it might work in mammals, and perhaps us. The authors speculate that if some smells (of food) can decrease lifespan, there must be other smells that might help increase lifespan.

My own take from all of this is that all of this comes from very good evolutionary reasons, all of which lead to reproduction. When times are bad (i.e. when there is too little food), it is probably a bad idea for any organism to reproduce, since it would mean a low chance of survival for the offspring. So, the body kicks in to back-up mechanisms, and goes on to prolong lifespans, till the times are good and the organism can reproduce in times of plenty. The same would hold true for smells of food, which would tell the mind that food is close by and so times are good.

Of course, humans are now so independent of food supply (almost guaranteed a steady supply of food, on a daily basis, and not hunting-gathering) that things must be slowly changing in us as well. Perhaps in a few thousand years more, we would have lost the responses to calorific restriction or smells of food.

Still, perhaps if you want to live extra long, avoid smelling those tasty, fried foods.

Me….. I think I’ll choose the good life, and head out for some beer and fries.

(If you want to read the complete research articles on smell and long lives, you can read it in Neuron, 2004, Volume 41, Issue 1, pp 45-55 and Science, 2007:Vol. 315. no. 5815, pp. 1133 – 1137

(Next week, I’ll write about newer studies based on calorific restriction leading to longer lives, where researchers have now found drugs that can activate the genes that appear to increase lifespan).

Tuesday, February 20, 2007

Wastage in labs

A recent news feature in Nature highlights the large amounts of energy wasted in science labs across the country (and world). Now, given the requirements of most science labs (which require specific lighting, extensive fume cupboards that circulate air, tissue culture hoods, plenty of electronic equipment and so on), the energy usage is expectedly more than most offices and almost all residences. However, what is rarely appreciated is the amount of energy wasted in many of these labs.

This news feature highlights many of those areas. An important point it makes is that the costs of this energy (in terms of electricity or water bills) aren’t paid by the labs themselves, but goes under some mysterious “overhead” expenses that universities bear. So, most scientists don’t realize how much the energy they use costs them. So, to quote a section from the article:

“ Laboratories consume between five and ten times more energy than office buildings — but they are also rarer and more diverse in design, making neat, generalized solutions to profligacy hard to find. Add that to concerns about safety and a lack of transparency in costs (few scientists know or care what their lab's electricity bill is), and you get a 'that's just the way they are' mentality. That's the mindset that the Labs21 programme, an initiative started by the DoE and the US Environmental Protection Agency (EPA), exists to challenge.”

There appears to be a slow realization that this is a problem, and newer equipment (with energy efficient ratings, or automatic adjustments to reduce energy when not in use). But to me this is not enough. What surprises me more though is an apparent contradiction between the amount of wastage (both of energy and of resources) in labs, and the personal lives of scientists themselves.

Many, many scientists I know are extremely conscious of the environment, resources and wastage in their personal lives. It is hardly unusual to see a university professor bicycling or walking to work, or driving a hybrid car, or recycling with vehemence. Many scientists I know are even going beyond the obvious, installing solar panels in their houses or using only bio-diesel or vegetable oil in their cars or boats. If a survey is taken on SUV ownership, I’m pretty certain a far lower percentage of scientists own SUVs than the average population at large. But in their labs there is invariably an excessive use of plastic (especially with pipette tips or pipettes), or taps are left running, or the lights remain switched on even when there is no one in the lab, or computers aren’t shut down after use…….I could go on for ever. It sometimes drives me nuts.

But why is this so? Is it only because we don’t see the costs of the wastage around us? Do we feel that the lab is somehow separate from the rest of the world (and our lives outside the lab)? Or, is it (like the news feature says) because that’s how it is, and so we just continue it?

Thursday, February 15, 2007

Trivial or wrong?

A scientist tries to unravel problems or identify new findings. Or so the idea goes.

Anyway, it is sometimes hard to find a "spectacular" or "breakthrough" problem to work on. It is often easier to find a simple problem to work on, making small, incremental, but sometimes inconsequential contributions.

On the other hand, while working on "breakthrough" ideas, you could sometimes come up with a hypothesis that is totally, absolutely wrong, and then waste years trying to prove it.

So, what would you do? Take a risk, make a prediction, take a stand and be spectacularly wrong, or be trivial, work on simple problems but with the comfort of knowing that life will be steady and without surprises?

Tuesday, February 13, 2007

Err, what? (a.k.a. "vote for me")

In news that is both flattering and a first step towards me ruling the world, it appears that this blog, Balancing Life, has been nominated under the best science/technology blog at indibloggies (though somehow my blog tagline, Everything Scientific, seems to have become the new blogname).

Amongst the other nominations in this category are a couple of blogs I always enjoy, Nonoscience and Sowmya.

I consider this to be a sign from the Pink Unicorn herself that it is time for me to start ruling the world, since I have no past history of winning elections (I couldn't even get elected as class monitor in 6th grade). Hence, this cannot be coincidental, but must be my time.

So, go vote for me here. (Apparently, there was a glitch in the sci/tech category, so you need to use this link to vote)

Vote for me!

If you don't....oh well, I guess I'll have to use plan B. I'll sulk by getting everyone I know to vote for the gawker, so that the millions of stunned fans of the phenominal Greatbong will hunt him down and destroy him. During the period of mayhem that results, I will rapidly make my move.

The world will be mine.

Muahahahahahaaaaaa............

Monday, February 12, 2007

All in the gut

Obesity, expectedly, is influenced by various different factors. A person’s diet, exercise, genes, other health conditions and various other factors influence how fat (s)he is. There have been plenty of studies describing the influence of all these factors on fatness.

But here’s one factor you probably never thought of.

The bacteria that live within the gut.


Most of us forget the fact that we are all walking ecosystems, and our bodies (particularly our intestines) are host to millions of bacteria of many different species. Most of these bacteria are extremely beneficial, sometimes essential for us, and allow us to efficiently digest food (that otherwise would be indigestible). And most of us have experienced some dietary discomfort after a course of antibiotics (which usually don’t discriminate between the good and the bad bacteria, resulting in some upset stomachs). But we would never have thought the bacteria within us could perhaps influence how fat we are.

But that is what two really interesting studies now tell us.

It all started from some observations in mice. If bacteria were harvested from normal mice guts, and then these bacteria were infected into lab-raised germ-free mice, the germ free mouse guts would become colonized by the bacteria, and the mice would soon rapidly gain weight. This seemed to be because the bacteria were now breaking down food that would otherwise be indigestible, and so the (once germ free) mice were able to absorb many, many more calories, and therefore gain weight. This got the researchers asking if the type of bacteria in the gut could perhaps influence obesity or weight gain.

To do their studies, they had a convenient model. There are some mice, where a certain gene, called the leptin gene is mutated. These mice are very, very fat (and there is now a booming field of studies on leptin and obesity). The authors decided to compare the microbial fauna in the gut of these mice with normal “lean” mice. To do this, the authors first put in a lot of work to “shotgun” sequence the total genes of the bacteriome from the different mouse guts, and found that over 90% of the bacteria in mouse guts were from members of two (out of 70 known) bacterial divisions, Bacteroidetes and Firmicutes. What the authors saw was that in the obese mice, the relative abundance of Bacteroidetes (compared to normal mice) was 50% lower, while Firmicutes were 50% higher. This was in spite of the fact that both groups of mice were fed the same diet, and same amounts of food.

So, the next question they asked was if the two different groups of bacteria could process food differently. Their results were even more remarkable. What they saw was that Firmicutes, the bacteria that were more common in obese mice, were capable of better “energy harvesting”, and had many more proteins that could help break down indigestible food than the Bacteroidetes, to make it available for the mouse.

But was this really playing a role in weight gain?

What the authors did next was to take bacteria from obese mice or normal mice, and inject these in to normal but germ-free mice. When they did this and allowed the bacteria to recolonize the germ-free mouse guts, they saw that the mice injected with obese mouse bacteria also ended up having a higher proportion of Firmicutes than the mice injected with bacteria from normal mice. And, the mice injected with bacteria from obese mice also ended up gaining more weight than the other group of mice!

You could dismiss this as being something in mice, but does it apply to us humans as well? The authors decided to address this question as well, and found a dozen obese volunteers and five lean volunteers to do their tests on. They found that the obese people, like the obese mice, had a greater percentage of Firmicutes, and less Bacteroidetes than the thin people. Finally, the obese people went on a low-fat/ low-carb diet for a year, lost a bunch of weight, and when tested showed a steady rise in the levels of the Bacteroidetes, and a decrease in Firmicutes (the “fat” bacteria).

So, obesity can alter the microbial balance in the gut, but apparently, altering the microbial balance can also alter obesity!

Of course, anything to do with obesity is going to raise a lot of interest, and people are now going to make grand proclamations, but this study doesn’t really say if the microbes in the gut are playing a major role in obesity across the world, or if they can be used to “treat” obesity.

I personally think going for a run and cutting out the crap-food is a far better way to stay lean.

But who would have thought, the bacteria in my gut are perhaps playing games with my weight?

(Nature 444, 1027-131 (21 December 2006) and Nature 444, 1022-1023 (21 December 2006))

Saturday, February 10, 2007

Dr. Doom or Lex Luthor

There, the results are out.

I'm smart, powerful but perhaps vain.


I am Dr. Doom


































Dr. Doom
73%
Lex Luthor
73%
Mr. Freeze
68%
Apocalypse
66%
The Joker
62%
Magneto
55%
Poison Ivy
53%
Riddler
50%
Green Goblin
49%
Juggernaut
49%
Kingpin
47%
Mystique
45%
Venom
43%
Catwoman
40%
Dark Phoenix
37%
Two-Face
21%
Blessed with smarts and power but burdened by vanity.


Click here to take the "Which Super Villain am I?" quiz...

Thursday, February 08, 2007

Recycling poison

Sometimes nature is just so remarkably cool.

This time, it’s one of the most remarkable stories I’ve read in a while. Though nature never ceases to amaze me, this story is quite something.

There’s this snake called Rhabdophis tigrinus, common in Japan and other parts of East Asia. Now, some (but not all) snakes of this species carry poisons in little sacks along the top ridge of their neck (called nuchal gland). These snakes, it turns out, are the brave ones. When threatened by hawks or other natural enemies, they arch their necks and expose these poison glands. This usually deters predators from biting or attacking them. What’s funny is that many of these snakes do not have poisons in their nuchal glands, so if predators come by they just run….er….slither away!


So, where does this poison come from, and why do only some snakes (of the same species) have the poisons? Some researchers asked the same question, and hypothesized that this snake could do something that is much more common in non-vertebrates (like sea slugs). Perhaps it acquires the poison from its diet.

These snakes apparently feed on toads (if they can get them). Many toads have poisons, called bufadienolides (which are supposed to protect them from predators). Not only does this snake apparently happily eat the poisonous toads, it recycles the toad’s own poison for personal use.

Some justice!

But the study itself that went on to prove this was very nicely done. In an article in PNAS, the authors first collected snakes from toad free islands in Japan, or islands where toads were very common, or regions where they occurred. They then sampled these snakes for bufadienolides in their glands, and what they saw was that the snakes from islands were toads were common had a lot of bufadienolides in their glands, the snakes from islands where there were no toads had no bufadienolides, and the snakes from islands which had some (but not too many) toads had an intermediate range of poison.

So then they (the scientists) went on to do more thorough research. They acquired hatchlings from snakes which did not have bufadienolides (were fed with fish). When the hatchlings were fed with toads they rapidly accumulated the poison in their glands, showing that the snakes could sequester dietary toxins. The researchers also further studied the type of bufadienolides in the snake glands, and this correlated with the type of toads the snakes were gorging themselves on.

It basically looks like this snake decided not to take the trouble of evolving poison glands. “Thank you ma’am, I get my poisons from my food.”

I never quite figured out why I loved National Geographic or Animal Planet so much. But this story just told me why.

Because it’s cool, that’s why.

(You can read all the technical details at the Proc. Natl Acad. Sci. USA website, doi:10.1073/pnas.0610785104, published online Jan 29)

Tuesday, February 06, 2007

Citizendom

Wikipedia has become such a part of my life that it is a rare day when I don’t visit the site to look up something. The site has grown to become a fantastic starting point to learn about just about everything. What’s more, it is mostly surprisingly accurate (Nature compared it to Encyclopedia Britannica and found it comparable in accuracy), given the fact that it can be compiled and edited by anyone, and most authors are non-experts in the field. However, this great strength, which allows the site to expand into every conceivable topic, is also a weakness.

It does not come with any expert authority, and there is little “incentive” for experts in the field to constantly contribute to the site.

Now, you might say the Wiki is just fine; there is no need for “experts”. Or you might say “an expert can contribute just as much as any one else, and that’s great”.

True. But there remain problems with that model. One of them is that experts might, just might know more about their chosen topic than another author, and might provide detailed information about a topic. But someone else might not like what appears on Wikipedia, and therefore edit it. Additionally, an expert author’s contribution (perhaps more carefully researched and referenced) is not valued any more than any other article.

Yet other completely expert driven efforts are far from flawless. Experts too may err, or have their own biases, or sometimes may not know specific areas of the field, or may base their articles on old data.

So, is there a way to create a resource as vast and powerful as wikipedia, but something that comes with more expert authority, greater reliability and importantly, more accountability, but still have widespread public participation?

It looks like the answer may be yes.

(going into deep announcer voice mode)

From the founders of Wikipedia comes a new, more exciting, more reliable and perhaps more powerful tool.

Welcome, Citizendom.

Citizendom is still in pilot (or in Google speak, beta) mode, but I think the model for the site is fantastic. It retains the large involvement of authors that Wikipedia has. But the difference is that the authors cannot remain anonymous and randomly edit sites. They work under real names, with real profiles (hopefully therefore increasing accountability). Additionally, all sections will be headed by editors, who will be experts in that field. The requirements for being an editor for a specific field are high. For example, editors in academic fields will need to have qualifications required for a tenure-track assistant professor position. But, importantly, like wikipedia itself, the editors don’t rule over the site. It will remain a broad public participation.

I think along with the high-profile open-access journal movement (led by the excellent PLoS journals) this may well become the defining moment of easy access to quality, reliable, “free” information for everyone who wants it.

Read more about Citizendom here. And like the wikipedia, you can be a part of it and shape its evolution.

Monday, February 05, 2007

Taking up Vitamin A

(The first of my posts for Just Science week, except that I forgot to signup for it).



Almost all of us know that Vitamin A is essential for us. Vitamin A plays a critical role in vision, bone growth and a whole bunch of other biological processes. Its one of the oldest known vitamins, and people even started synthesizing it in the 1940s. We know what it is important for, where it is stored (mostly in the liver), how much we need and many other things. We also know that Vitamin A is delivered to other cells and organs in the body by a protein called retinol binding protein (RBP) (Vitamin A is found in the body as retinol).

All well and good. But one question has puzzled researchers till today. How does Vitamin A get inside cells, specifically? If it were simple diffusion or permeation, it would be hard to specifically send the Vitamin A only to cells that needed it (like the retina), and not just distribute it all across the body. Part of the puzzle was explained by the fact that RBP bound Vitamin A tightly, and the serum in blood transported the RBP (with Vitamin A) to the cells that needed it.

But how did the Vitamin A enter the cells? In other words, how did RBP know which cells required Vitamin A, and even if it did, and went to those cells, how did the Vitamin A get inside those cells? The answer lies in a Vitamin A receptor.

Receptors specifically “receive” molecules (they could be vitamins, minerals, other proteins, other small molecule chemicals, anything), and subsequently carry out some specific effect. In this case, scientists have long speculated the existence of a receptor in cells for the RBP, with this receptor being found in many different cells. The idea was that this receptor specifically bound to RBP, and then mediated Vitamin A uptake from the RBP (bound to Vitamin A). But, even after so many years, people didn’t know what the receptor was, and what it did.

Now, finally, we know what the Vitamin A receptor is.

Researchers have identified a receptor that binds RBP, and mediates the uptake of Vitamin A.

(That’s the summary of the post. Read on, to see how they figured it all out).

One reason I really liked the study was because it was a very elegantly done, using classic, “old-school” biochemistry (which is increasingly uncommon). There were a couple of reasons why the RBP/Vitamin A receptor was hard to find. There was a possibility that it had a weak, transient interaction with RBP, so if people tried to purify RBP, they would not have found the receptor attached to it. Another possibility could be that this receptor itself could be fragile or easily degraded if purified from the cell. Yet another possibility could be that it is just darn hard to purify. After all, if it has to receive the RBP protein, it has to be on the outer surface of a cell, embedded in to the cell membrane. It could well have been all these reasons combined.

What the authors of the study did was first to stabilize the RBP-receptor interaction. They did this by an old, old technique called crosslinking, where a chemical agent was conjugated to RBP, and this was “linked” to whatever RBP bound, by activating the crosslinking by ultraviolet light. After that, the authors could solubilize the membrane and then purify RBP, with the assumption that what ever was crosslinked to it would also purify out with RBP. They did exactly that, and found an unknown protein crosslinked to RBP.

Now, to identify this protein, they used an analytical technique called mass-spectrometry. This technique requires the ionization of whole proteins, as a first step towards identifying the protein. Some proteins are notoriously difficult to ionize, because they are extremely hydrophobic (for the non-chemists/biologists here, remember your high school chemistry, where you learnt about “polar” and “non-polar” compounds? Non-polar compounds don’t dissolve easily in water, and don’t carry a charged end). This receptor of RBP turned out to be extremely hydrophobic as well. So, they could identify only one peptide (a protein usually has many building blocks called amino acids, and a few amino acids make a peptide. Sort of like a sentence in a paragraph or page). Luckily for them, this one peptide was unique enough to match with only one protein (ah, the wonders of the human genome), so they were able to identify this protein.

It is called STRA6.

In the rest of the study, the authors go on to characterize STRA6, and conclusively prove that this indeed is the receptor for RBP, and the means by which Vitamin A is taken in to the cell. They find that this protein is in the cell-membrane (with eleven membrane spanning regions). They find that this protein is truly unique in its architecture, and no other proteins in mammals resemble this protein, even in part (most proteins use common “parts” or domains and combine them to gain their specific functions). Importantly, this protein does substantially enhance cellular Vitamin A uptake (they use radioactive vitamin A to measure how much is taken up, and also use mass-spectrometry to detect it directly). Also, this protein is found only in regions where there is a known or predicted role for vitamin A. This was a very satisfying study to read, since the authors take pains to conclusively prove (from various angles) that this protein is indeed the vitamin A/RBP receptor. They show that (a) it binds RBP, (b) it increases vitamin A uptake within cells and (c) it is found only in places where vitamin A is needed (a single observation does not prove a scientific hypothesis, it needs to be systematically proven).

I particularly liked this paper as it provided a reminder of how powerful classic biochemistry and pharmacology is even in modern, breakthrough discoveries (too many scientists seem to do “flashy” science, using new technologies, forgetting the strengths of classic methods). It’s the kind of science breakthrough I dream of making, done the way I would like to (or how I imagine my graduate advisor would have done).
You can read all about it in Science magazine (Science 25 January 2007, DOI: 10.1126/science.1136244).

Saturday, February 03, 2007

Counter intuitive or plain stupid?

Living in Dallas, it is hardly uncommon to open the newspaper and read about some oil or coal or automobile company lobbying the government for something or the other. Take this example of lobbying by companies who want to continue to build and run (poor or low efficiency and highly polluting) coal powered plants.

This story is repeated across America, with American car companies wanting subsidies and freebies to continue making lousy, inefficient cars, or oil or coal companies wanting to continue to build and operate higly polluting, inefficient plants.

The money they spend on lobbying comes to a few million dollars. Usually, after a few years, they end up spending many more millions either cleaning up the mess they caused, or being forced to rebuild from scratch (with more efficient technologies). Sometimes, the losses they post are staggering.

But still, they continue to lobby to make crap.

Now, wouldn't all this money that the spend on lobbying or cleaning up messes be better spent on researching new, better technologies that are more efficient, and likely to last longer with lower recurring costs? Clearly, the people running these companies must be smart. But this, even intuitively, seems to be a better long term solution. Are these companies incapable of seeing beyond the next quarter profits, or am I just plain stupid?