A Story of Glowing Maps

The Japanese didn’t have GPS during World War II, at least not in the form that we’re familiar with today.  If ground troops in the Pacific wanted to look at a map, they had to shine a light on it, and that was rather detrimental to their survival prospects if they needed to know where they were while conducting a secret night time operation.

Luckily for the Japanese soldiers, one thing the Japanese knew a good deal about was ocean life. In particular, a crustacean they call an umi hotaru or “sea firefly”  has the unique property that if you prod it, it glows. If you crush a bunch of these little guys up, and pour water on them, you can create a glowing sludge that you can put on your hands. A glow that is dim enough to not be noticed in the field, but bright enough to read a map by.

When the atomic bombs fell on Hiroshima and Nagasaki, it effectively ended the Japanese soldiers’ need for glowing maps. But a young man who had been working at a factory only 15 miles away from Nagasaki when the bombs dropped, would ensure the sea firefly retained its place in human history. A decade and a lustrum after the war, this man, Osamu Shimomura, was studying at Nagoya University when his mentor,  Yoshimasa Hirata, gave him the task of figuring out how the sea firefly glowed.

Sea fireflies. Image from http://mytechnologyworld9.blogspot.com/2010/11/sea-creatures-used-as-light-for-reading.html

Sea fireflies, similarly to the fireflies we’re more used to, glow, in part, because of a protein named luciferin.  When oxygen binds to luciferin in the presence of another protein, an enzyme called luciferase, the molecule glows. Even though the sea firefly had been studied for a number of years, no one had been able to purify its luciferin because it was so unstable. If you’ve ever had a firefly splat on your windshield, you’ve observed this instability first hand. The firefly guts glow, but they quickly fade to nothing. When the firefly splats, its luciferin binds with oxygen in the air, causing it to glow as it degrades, but it’s used up after only a few moments. In order to purify the luciferin from the sea fireflies, Shimomura had to take powder from the crushed creatures and distill it using a complicated apparatus (pictured at right), then get it to crystallize in a special solvent, all before too much of it degraded into uselessness. It was tough work, but Shimomura finally did it, and published his results in a scientific journal that got the attention of Frank Johnson, a professor at Princeton University in the U.S.

At Princeton, Johnson and Shimomura worked on figuring out how jellyfish glowed. At the time, the popular theory was that every living thing that glowed used some form of luciferin and luciferase, but try as they might to purify luciferin  from the jellyfish, they weren’t able to do it. The problem was that the jellyfish they were looking at didn’t use luciferin at all, but a completely different protein.

Jellyfish glowing mechanism. Image from http://www.conncoll.edu/ccacad/zimmer/GFP-ww/shimomura.html

Shimomura suspected this might be the case and looked into the possibility on his own even while Johnson obsessively pursued the luciferin angle. After a tense period of disagreement, Shimomura discovered that the glowing was actually caused by two different proteins: one, which Shimomura and Johnson named after the jellyfish they were studying, (aequorin) and another, present only in trace amounts, which they called simply “Green protein,” because it glowed green when placed under an ultraviolet light.

Thing was, although the green protein was present in only trace amounts, it had a dramatic effect on the bioluminescence of the jelly fish. Aequorin, the more numerous protein, glows blue in the presence of calcium ions, but instead of glowing blue, as one might expect, the jellyfish glow green.  What is happening here is that the blue glow from the aequorin was making the green protein fluoresce green. This was a very interesting property for a lot of researchers and so the green protein was studied in several other labs, and was soon officially renamed “Green Fluorescent Protein” or GFP.

Shimomura and his colleagues spent many years gathering enough of the protein from the jellyfish near Princeton to properly analyze GFP, isolating  the part of the protein (the peptide) that was responsible for its fluorescence. Such fluorescent peptides are called chromophores.

GFP is unique among fluorescent proteins in that its chromophore is within the actual protein, as opposed to being in a compound attached to the protein. This means that if you can copy the DNA that’s responsible for making the protein, you can recreate the protein in all its glowing glory in just about any animal you care to genetically modify , and indeed,  Douglas Prashar and his colleagues  managed to do  just this in 1985, “cloning” the protein so that other, animals could produce the protein. This allowed research on GFP to continue, even as  the jellyfish it originally came from became much harder to work with due to decreased populations.

The nematode worm C. Elegans

In 1989, a marine biologist who spent many of his summers studying at the same research facility that Shimomura worked at, was giving a lecture on fluorescent proteins and bioluminescence when one of the scientists in attendance, Martin Chalfie, had the idea that he could maybe use GFP in his research on nematode worms.

Nematodes have bristles on their bodies, which normally make them very touch sensitive. The system that allows them to feel touch is governed by a very fast molecular motor, operating at least ten times faster than the molecules responsible for vision in humans and other animals. Chalfie was studying how this touch system worked by comparing normal worms with worm mutants that lacked the gene that produced the molecular motor. The problem was that the only way to distinguish between the mutant worms and the regular worms was to either kill them, which would make it impossible to check their touch sensitivity, or to tickle them with a hair, which kind of defeated the purpose.  He wanted to know which worms were touch sensitive, not just that some were and some weren’t.

One thing that nematodes have going for them is that they are transparent. Chalfie realized that if he could get a fluorescent protein to show up wherever the molecular motor was produced, he could easily distinguish between the mutants and the normal worms without having to kill them, because the worms that had the fluorescent protein would glow.

In 1992  when Chalfie and a graduate student of his found out that Prasher had been successful in cloning the gene for GFP,  they contacted him and worked out how to express the GFP gene in bacteria. To their delight, GFP didn’t require any other molecules to get it to glow after it was produced from the gene. All Chalfie had to do was insert the gene into the bacteria, and it made the bacteria fluorescent. That meant that GFP could be used in other organisms easily.

Chalfie’s wife, Tulle Hazelrigg, gave the next contribution to the study of GFP by showing that fusing the molecule to another protein causes that other protein to be fluorescent as well. This meant that rather than simply labeling mutants versus normal animals, researchers could see exactly where the proteins showed up in the animals they studied.

Finally, Roger Y. Tsien, a Chinese-American biochemist working at Berkeley, California improved the GFP molecule by mutating the gene so that the GFP that was produced was brighter and could be seen with the fluorescent scopes that were already widely available in many different labs. He also was able to make GFP mutants that glowed red or yellow instead of green, allowing several different proteins to be viewed at the same time. This gives scientists a glowing map of where all the proteins they want to look at are showing up in their samples.

One of the most remarkable uses of this technology is in the Brainbow technique, developed by Jean Livet, Joshua R. Sanes, and Jeff W. Lichtman, which labels each neuron in the brain of a research animal individually with a separate color formed by a combination of fluorescence molecules.

An image of a rodent brain using the brainbow technique

So we’ve gone from glowing maps of battle grounds, to glowing maps of the brain all in the span of some sixty years.

Osamu Shimomura, Martin Chalfie, and Roger Y. Tsien all received the Nobel prize in chemistry in 2008 for their work on GFP. Shimomura has retired to emeritus status, but Chalfie still works on worms, and Tsien still works on sub-microscopic molecules. They have all changed the world.

My information for Osamu Shimomura came primarily from his 2008 Nobel Prize lecture.I got Martin Chalfie’s story from an interview conducted with him on the podcast Futures in Biotech. I left quite a bit out for simplicity’s sake, so I suggest giving these sources a look if you’re interested.All other sources are available through the hyperlinks I have provided in text.

Big Dumb Aliens

The alien Mo-Ron from the show Freakazoid

Last night I watched yet another movie with big dumb aliens in it, Cowboys and Aliens. Don’t get me wrong, C&A was a pretty good movie. I’d give it a 7/10. It’s fun, and it turns out Olivia Wilde is a sexy alien, which I always kind of suspected. But it seems that if an alien isn’t humanoid, they have to be some kind of horrible beast that kills people for some inadequately explored reason. Just listing some recent ones there’s Cowboys and Aliens, Super 8 (7/10 I’ve downgraded it from a previous score), Battle: Los Angeles (6.5/10), and the tv-series Falling Skies (4/10). Not so recently there was Independence day, and who can forget the aquaphobic aliens in Signs. Basically ever since the movie Alien, there’s this trope of big dumb aliens attacking us, that kind of has me peeved.

In Alien it made sense. The Giger alien monster didn’t come to us, we came to it. It was a creature, not an intelligent being, at least not in the first movie or so. But in all the movies I listed, to a greater or lesser extent, all the aliens come from innumerable light years away using technology we can only dream of, and when we see them we are distracted by how coldly they are separating our heads from our torsos using their serrated appendages.

There are other cases where this makes sense. I included Battle: Los Angeles because the aliens are big and burly and are attacking us, but in that movie they were just the soldiers sent to Earth by the weaker, presumably nerdier ruler aliens. In fact for all we know in the movie the soldiers might even be another species conscripted into battle by their previous conquerors.  I still call Big Dumb Alien in B:LA, though,  because there’s something missing in it that’s missing in all of them. Communication. You can’t really develop any advanced level of technology without communicating. You can’t organize the concerted invasion of a planet without it either. And yet we hardly see the aliens communicating at all in Big Dumb Alien movies. Not to themselves, and certainly not to the humans.

Super 8 is a little bit of an exception here. The alien does eventually communicate with a human and vice versa, but, I still include it, because the alien acts like a savage animal throughout most the movie. It can make people understand it if it touches them. Fine, but as my brother asked after he watched it, why doesn’t it just touch everybody then? Why not do that instead of killing people, or tying them up in some cocoon thing?

The aliens in Falling Skies might also be considered an exception because some humans eventually find out they communicate on radio frequencies. And they can also use children as cyranoids, speaking through them against their will. But why not do this all the time from the start? Their goal is to rape the Earth of its resources, fine. But it isn’t exactly working out that well if your operations keep getting attacked by the indigenous population. The idea is that they’re supposed to act like European colonists, but the European colonists had Indian guides. They didn’t start out mindlessly attacking natives. They ate with them, traded with them, gave them small pox that decimated their population, and THEN they killed them.

The other thing I don’t like about Big Dumb Aliens is that they aren’t just dumb, but big too. It just seems to me that any creature that can kill other creatures easily probably has little incentive to develop an advanced civilization. We humans have got opposable thumbs and our brains and that’s pretty much it as far as physical advantages go out in the wild. We have martial arts, but that’s a developed skill requiring technology. We have weapons, but that’s already technology right there. Just us, by ourselves, we ain’t much. That’s why we had to use our heads and work together to survive.

I just have a hard time believing that something with razorblades coming out of its armpits would ever try using a rock to kill something. The whole premise of these naked creatures being intelligent enough to travel through space seems off to me. It’s possible, but it just doesn’t seem likely. The whole reason we wear clothes is because we’re vulnerable. I just tend to think that if we didn’t have to wear clothes, we would have never invented the internet.

One of the best things about Cowboys and Aliens is the alien technology. There’s a nifty alien gadget that melts gold and floats it, dripping, up to receptacles that move it to the core of their ships, presumably giving them power somehow. Their ships aren’t just slightly tweaked versions of our aircraft, they look completely different and yet move how you might expect them to move. There’s a strange feeling I got while watching where I forgot that what I was watching was impossible. The mother ship is buried in the earth (which also seems to be a running theme in these movies now that I think about it) with a large part sticking out of the ground that looks similar to the rock mesas around it in the desert. When the camera first showed it, my eye just sort of took it in with everything else. There’s the plain, the sun, part of a mesa, an alien space craft, another mesa, a horse…wait what? The arm band thingy too, was different, yet it worked so naturally I wouldn’t have been that surprised to find out Steve Jobs or somebody designed it.

But all that care that went into the tech is rather wasted on the big dumb aliens that use it. A human gets a hold of one of their arm guns. Do they organize a group to go after that human and retrieve the weapon? Nope! They just carry on, tra la la, business as usual, kidnapping humans, making them watch television until they forget who they are and then cut them up and kill them for no real reason.

Of course in the movie, the humans are equally stupid. Okay, you know the aliens have these nifty arm guns that are the only things that seem to do them any noticeable harm. You manage to kill a few of the aliens that have the arm guns by luck and guile. What do you do? Keep shooting bullets so you can watch them ricochet off their impenetrable armor… WRONG! Cut their arms off and get their freaking arm guns! What’s wrong with you people!

…But I digress.

Basically the point I’m trying to make here is that if you’re going to write a movie where aliens are going to invade earth, take a few moments to think on things from the aliens’ perspectives. Yes, having a smaller alien body part come out of a larger alien body part is creepy, but how does that help the alien? Is it being creepy on purpose? Is that the alien’s way of saying hello? How about showing that the alien uses the smaller body parts for sophisticated tasks requiring a lot of dexterity or something? Anything. If you can let us know something about where the aliens come from and especially if you can show them working out some form of counter strategy to what the humans dish out instead of them just being evil, that will make the story so much better.

Just a thought.

Switchblade Pisces pt1

Next>Latest>>

There’s a beautiful woman in my apartment. Unfortunately, she’s about to kill me. I suppose you got to take the good with the bad. The only reason I’m not already dead is that the floors of my crappy efficiency apartment are so squeaky they’re pretty much ninja proof. The woman’s on the other side of the room right now wearing khaki shorts and a light blue sleeveless top. She has a utility belt and her milky blonde hair is in a braid. The odd thing is that she’s got these two small, black boxes on the top of her head. That and she’s wielding two knives in her hands.

I’m probably going to die.

She advances on me slowly. I’m still sitting in my swivel desk chair, turned around from my laptop. I wonder what James Bond would do in this situation. He’d grab the girl’s wrists and seduce her into a kiss, and then she’d tell him everything as she languished beside him on silk sheets. And in the next morning she’d be conveniently dead.

Well that sounds nice, even if it seems a little like retroactive necrophilia. I stand up, my hands out like I’m about to catch a beach ball, and I clear my throat, preparing my best Bond impression. “Um…could you stop please?”

Yes, I’m afraid that was more or less entirely unlike James Bond. Particularly the “um.” I’m pretty sure he never ever said “um” in his whole made up life. Then again, whatever I said seems to be working.

The beautiful woman has stopped.

Her skin is perfect, except for a thin, barely visible scar across her right cheek. Her eyes are an enchanting shade of purple, and they are dilated. I read somewhere that if a girl’s eyes are dilated, it means she likes you.

What does it mean if a girl has purple irises? Oh yeah, that she wears contacts. I haven’t seen colored contacts much since the late nineties though, and while I’ve heard of platinum blondes before, the girl’s hair seems more soft and liquid than shiny. I’ve never seen hair like that. It definitely isn’t bleached, or at least I don’t think it is. Who knows maybe there’s some new product out there that I don’t know about.

I’m not sure what to make of the two black boxes protruding out of her skull on either side of her braid. I could almost convince myself they were decorative bows, except for the blinking LEDs and the little computer fans whirring on the sides of them.

“Could you, ah, drop those knives?”

“No,” the girl says in a melodious soprano, “I cannot.” There’s an uncomfortable pause. Then the girl says. “They are surgically attached to my body.”

“Huh?” I ask, intelligently.

By way of answering my question, the girl straightens and lowers her weapons. Then, in a motion so quick I almost don’t catch it, she retracts the blades and the handles into her wrists.  “What the… who the hell are you?”

“I am a Pisces,” the woman says as if that explains everything.

Next>Latest>>

Aquamarine

The general thrust himself into the lab, marching past the intern who had greeted him at the entrance of the building. He had two aids with him, one male one female, both of them looking like they had been manufactured somewhere, despite being perfectly human. They wore nondescript suits and were perpetually muttering things into their devices. The man himself had silver hair cropped in a military style and shoulders that spread out from his head like the wings of some bird of prey. He wore his uniform from his days as a general festooned with medals in the manner of someone you didn’t want to mess with.

Charles Gentry waited for the man and his entourage to approach from inside his clean room suit. He could hear his own breathing, feel the humidity of it as it threatened to fog the clear plastic of the helmet. The plastic was treated, so it would be fine, but there was still the feeling that condensation would form at any moment.

“Good morning, Dr. Gentry,” growled the general, all pleasantness stripped from the pleasantry, “Is there a safety issue I wasn’t informed of?”

“No, sir.” Charles studied the general’s two assistants, who were scanning the room continually but not appearing to see anything. “This isn’t a hazmat suit, it’s for the clean room. I’m in and out of there a lot today, so it’s easier just to keep it on. I just decontaminate the outside of the suit before I go in. You’ll see some of the other researchers doing the same. It’s uncomfortable, but it keeps things moving.”

The general raised his head up slightly in a half nod. The man valued efficiency, especially if it came at the expense of comfort. “Let’s be quick about this then. You say you have a prototype ready?”

It was Charles’ turn to nod. “We keep it in a sort of airlock between the wet lab and the clean room. It’s in a stable form, so you don’t need a clean suit to work with it, but both sides of the lab need access to it for experiments.” He walked, inviting the general to follow him. “ I appreciate you coming down here. Our funding is about to run out and we can’t run the risk of going through the usual channels.”

“I understand your research may prove a security risk. I’m warning you, though, this better be good, Dr. Gentry.”

“Oh it’s good alright,” Charles said as he reached the door to the antechamber. He couldn’t help but smile as he continued, “It might just mean the end to all war.”

The general’s thick eyebrows came together in a frown. “What do you mean? Is it a bomb of some sort?”

Charles realized he let out more than he had intended. He glanced at the general’s assistants. “What’s their security clearance?”

The general studied Charles for a moment, seeming to weigh the risks. He took a percussive breath. “Michaels, Chamberlin, wait here for me. I have a feeling this won’t take long.”

The two assistants rolled their eyes in tandem and stepped back as if security clearances were the bane of their existence and life would just be so much easier if they could just be allowed to follow their boss indefinitely.

“Five minutes at the most,” Charles reassured the general. “And you will be impressed; I can guarantee it.”

The general gave his half nod again and Charles yanked open the door to the antechamber, pulling against the negative pressure caused by the air being sucked out of the chamber and through the filtration system. Charles hoped the general didn’t notice. Then he realized the man probably wouldn’t realize the implications even if he did. It was too late anyway. He was in the antechamber with Charles, alone.

“It’s not a bomb,” Charles pulled open a fume hood and withdrew a vial of a dark, syrupy, aquamarine substance to show the general. He unscrewed the plastic top. “Some would call it a namcub.”

“A what shrub?”

“A self-fulfilling prophecy, an incantation that affects the minds of those who experience it.  It’s basically liquid hypnosis.” Charles could tell he wasn’t getting through, so he tried one more explanation. “With this substance, you can hack somebody’s brain.”

The general immediately seemed to lose all interest. “We already have drugs for that sort of thing. Brainwashing techniques have been around since the nineteen-fifties.”

Charles shook his head, but the movement wasn’t that visible while he was inside his suit. “No sir, not like this. Look at it. Look how clear it is, how it moves just like water.”

“Yes it is clear. It looks just like water. But that’s not the point. We’ve tried these mind drugs in the past. They don’t work.”

Charles lifted the vial. “This isn’t a drug, sir. It’s billions of synthetic organisms and nanomaterials in a nutrient bath. Smell it.”

The general brought the vial to his nose and sniffed. He scrunched his nose at the sharp scent of sulfur and alcohol that burned his nostrils.

“No odor at all, right?”

“Right,” the general agreed as if it were obvious, “The problem is even if it works, it’s still not as effective as a spy with their brain intact. Drug induced sleeper agents have a bad habit of staying asleep.”

“But, if you could get control of specific people in power, if you were smart about it, and remained hidden …”

The general laughed, took the vial and drank the contents in one gulp. “Go ahead, Son. See if you can do it. See if you can convince the president, congress, the American people, that they’ve been a bunch of idiots and they need to listen to you. See if you can change one thing for the better and not have it get corrupted, perverted and spat back into your face. Go ahead, show me how to rule the world. Because I sure as hell haven’t been able to figure it out.”

Charles took a breath as the enormity of what he was trying to do hit him. Then he let it out with slight chuckle. “I hear what you’re saying, sir. It is a difficult problem to solve. That’s why I feel education is so important.” Charles put an arm around the wide shoulders of the older man. “It’s our children who need to learn to rule the world after all. In fact, I think education is the most important issue facing our country. Don’t you agree?”

“Yes,” the general said, “I agree.”

Charles smiled and patted the man on the back before opening the door and letting him out of the antechamber. He told himself he was being responsible, making sure his technology wasn’t used by the wrong people. And maybe the government would concentrate a little more on education.

What could be wrong with that?

Charles tried his best not to answer that question.

Immunohistochemistry

Diagram of how an atomic force microscope works

So there’s this amazing protein you want to study, and it might very well change the world, but you have a problem: how do you study the protein when its too small for even a microscope to see?

There have been a number of solutions to this problem over the years, many of which are still being used. You could, for instance, study the protein’s effects by adding controlled amounts of it to a sample, or you could keep an organism from producing the protein  through surgery, drugs, or geneticsand see what what happens when it isn’t there. More directly, the obvious solution is to get a better microscope. What do I mean by a “better” microscope? Well, although there are some drawbacks, there are some microscopes that can give much higher resolution and/or provide added information about what you’re looking at.

One example of this is an atomic force microscope. How this works is that a small needle on a cantilever connected to a computer is dragged across what you want to look at. The computer then measures all the bumps that the needle encounters and gives a visual representation on the screen. As you might suspect this method has a number of drawbacks, (the cantilever is fragile, samples have to be specially prepared, etc) but it is possible to identify single atoms using this method.

Another type of microscope that can help you find a protein is an electron microscope. The idea here is to use electrons instead of photons to look at a sample. There are a number of drawbacks to this idea as well, for one thing, samples usually have to be “fixed” with a chemical such as Osmium tetroxide  and this can sometimes change the way things in a sample look. However, here the drawback can also be a good thing. What “fixed” means in this case, is that the molecules are attached to the things around them, and so aren’t going to move around all over the place like they would normally. If you want to see stuff moving around, you’re out of luck, but often you want to see where something is at a particular time and you don’t really want it to be free to wander.

There is another benefit to using electron microscopes. Parts of a sample will be darker depending on how electron dense they are after they’ve been fixed.  the electrons that the microscope uses to scan the sample will bounce off of that part of the sample, causing there to be a dark region. It isn’t always easy to tell which molecules will be more electron dense than others, but there are ways of making it easier. For one thing, if you have a molecule that you know is electron dense that you also know will form a bond with the protein you are looking for, you can add that to your sample and then you can compare the dark regions in the treated sample to how an untreated sample looks. The dark regions that appear in the treated sample but not in the untreated will most likely be your protein.

How confocal microscopy works

This trick also works with fluorescent and confocal microscopes. These microscopes shoot  beams of light at a constant, controlled frequency on the sample, causing some molecules to fluoresce, emitting light at a slightly different frequency. Confocal microscopes have the added benefit of being able to control where exactly the lasers focus so that it can show not only where something is in terms of up, down, left, and right, but also where it is in terms of depth. Once again, if you know a molecule is fluorescent and that it binds to the protein you’re looking for, you can add it to your sample and then check it out in the fluorescent microscope to find your protein. That’s great, but how do you find a fluorescent molecule to bind to your protein?

Diagram of antibody production

Well, your body has a ready-made system for finding molecules that will bind to proteins that has been tested over millions of years of trial and error. The immune system. If a virus or a bacterium enters your body and starts causing problems, your immune cells will start producing antibodies for the proteins that are present on the surface of the intruder, so that if it shows up again, it will be dealt with before it can cause any damage. Antibodies are large (by protein standards), y-shaped molecules produced by white blood cells. There are binding sites at the ends of the smaller arms of the y that bind to specific parts of a molecule. The binding sites act as a sort of lock, where the key is the part of the molecule the antibody binds to. There are a huge number of different binding sites that are available due to the genetic information encoding the antibodies getting shuffled and mutated all the time. When a cell in the body gets stressed, it sends out a signal that a white blood cell(a macrophage to be specific ) can respond to. This white blood cell then invites another cell (a T-cell) to take a look.  This T-cell will then go out and talk to another cell (a B-cell), which has a catalog of antibodies available for production that the T-cell can peruse by seeing if the peptide, or protein part, that’s in the stuff the macrophage ate, is also in the B-cell. If any antibodies from the B-cell  bind to something in the T-cell saw in the macrophage, then the B-cell knows to produce more of that kind of antibody. After that, wherever an antibody encounters its target, it triggers a response from other white blood cells.

Sometimes a cell might be stressed, but the antibodies will bind to something that isn’t the cause. Molecules, from peanuts, pet hair, pollen or just about anything might happen to be present in greater quantities than the thing that’s really causing the problem. This is how allergies happen.

That’s the bad news. The good news is that because antibodies can be found for almost any kind of molecule around, scientist can used lab animals to produce antibodies to the proteins they want to study. Furthermore, by manipulating the genetics of the animal, they can cause each antibody to be attached to a fluorescent molecule. The antibodies can be stored in a vial in a freezer and transported cold to labs all over the world. All a scientist needs to do then, is bathe whatever he or she is studying in a dilution of the antibodies, and then look at the sample with a fluorescent microscope. Wherever the sample fluoresces, that’s where the protein is.

This process is called immunohistochemistry. Immuno- because it deals with antibodies from an immune response, histo- from the Greek for tissue, and chemistry because it deals with the binding of molecules.

Antibody production diagram is from A Positron Named Priscilla: Scientific Discovery at the Frontier (1994) National Academy of Sciences (NAS) ( http://www.nap.edu/openbook.php?record_id=2110&page=69 ) all other images from wikipedia.

Super8review and excuse

I recently saw Super 8 at the theater. It was great, like a mix between E.T. and Godzilla, I give it a 8.5 out 10.Watching it gave me the same feeling as riding a ride at Disneyland or Universal Studios. I always felt like there was something else going on. There’s practically a war going on through out most of the movie, but the camera focuses on the children who are the main characters. You see a lot of the effects of the war without ever seeing what caused them. In one scene the wall of a room explodes away from the kids unexpectedly. Surprising, and it keeps things interesting. At first the alien didn’t seem very intelligent. It acts like some kind of monster through most of the movie, which I find a little annoying, but the movie makes up for it by the end.

I originally wrote a more extensive review of Super8 as well as some other movies, but it got lost when I hit ctrl-c instead of ctrl-v. My family and I got back late today from garage sale-ing. We ended up going all the way (about an hour) to Brentwood to go to an estate sale, which, it turns out, wasn’t going to happen until tomorrow (my brother’s fault:-)). We went to some other places though, so it wasn’t too bad. I got a bunch of old books, a portable tape player and a CD holder.

Brains

It was potato chips. Potato crisps if you’re British I suppose. Doesn’t really matter. They were ubiquitous. They were in every household. The plague rats of the twenty-first century, and nobody suspected.

Now almost everyone is dead. Including me.

Except…Wait… I’m thinking! The plague must not have completely killed me! I blink. My vision is blurry, but it slowly begins to clear. A lady is cornered in an alley by a cadre of my fellow plague victims. Zombies. She wields a shotgun. She shoots a zombie in the chest, but of course all that does is knock it back a few feet. I suppose she didn’t watch any horror movies before the plague. Probably thought they were too gory, or a waste of time.

Typical.

She’s thin, kind of bony, and she wears dark rimmed glasses. The right lens has a crack in it. One leg of her slacks is in tatters and her blazer is ripped. She was probably a very severe looking woman before the plague. Very conservative. The kind of person you wouldn’t expect to eat potato chips. I guess that’s how she managed to survive.

It’s strange, but I think the post-apocalyptic look suits her. Her hair coming out of her bun in wild wisps, her eyes wide, I doubt if she would look as attractive all tightly put together like she must have been before.

I realize I’m shambling toward her. I try to slow myself, but I still don’t have complete control. Using all my will power I manage to raise my arm. It hurts like hell. My arm shakes. It looks like I’m reaching for her as I stumble forward.

If I can just communicate somehow, maybe I can help her. Maybe I have an immunity of some kind to the disease. I struggle to bend my elbow. To move my fingers. My joints creak with the effort. I do a slow wave. I move my dry tongue around in my mouth trying to work up some saliva. I try to talk, but my first effort comes out only as a moan. I try again, but instead of “Hey don’t kill me, I’m not like the others!” or “I’m not quite dead yet!” it comes out as “Braaiiiinsss!”

“Thanks for the tip,” the lady says, smirking and looking crazed. She re-chambers her shotgun. She apparently is taking what I said as advice on where to aim.

My eyes go wide. My lips crack in a dozen places as I mouth the word “NO,” and I try to move away as she aims the barrel of her weapon at my head and-

Molecular motors

At this very moment, inside every cell of your body, there are thousands, even millions of machines, so small that they can’t even be seen with a conventional microscope, performing tasks in mere fractions of a second without any direct supervision. There are tiny molecular robots working together inside us to accomplish goals that scientists are only beginning to understand, every moment, of every day, through out each of our lifetimes. And it’s not just in our bodies. In the bodies of every living thing these things are active. They are, in fact, required for the basic prerequisites of life, yet individually, they are nothing but dumb molecules, practically inert unless the molecules they interact with are present. These things are called molecular motors.

There are a bunch of examples of these and every time I think about them I’m amazed. I just have enough space to talk about maybe two of them, but really almost all molecular motors rely on three things: energy, tubes, and molecular components.

Chemical structure of ATP

The usual form of energy for molecular motors, the twenty dollar bill in the economics of proteins, is ATP. ATP stands for Adenosine triphosphate, and its called that because it is a molecule made up of adenosine attached to three phosphorus atoms (called phosphates while they’re still bonded to a certain number of oxygen atoms) arranged in a line. If proteins need energy for a reaction, they get the energy by lopping off one of the phosphates of an ATP. ATP then turns into ADP (adenosine diphosphate) and the energy that was stored in the bond between the phosphate and the rest of the molecule goes into whatever is needed by the molecular motor or by the reaction that’s going on. When a molecule snaps off a phosphate, the phosphate is bound to that molecule for a while and the molecule is said to be phosphorylated.

This might be a little boring in itself, but the cool thing is that so many different reactions inside a cell depend on the same ATP molecule. Almost every reaction between proteins involves a phosphorylation or a de-phosphorylation. When you eat food, what you’re really doing is supplying your body with ATP.

Adenosine is actually one example of a class of proteins called nucleotides. They can all carry phosphates, though adenesine and guanine are the ones typically used for energy. The reason nucleotides are called nucleotides though, is that they are all present in DNA, which is found in the nucleus of a cell. There are the four typical nucleotides you might remember from high school biology (Adenosine, Guanine, Thymine, and Cytosine) and then there is another that is only present in RNA, uracil. DNA forms a double helix, or a twisted ladder, with each nucleotide forming a rung in the ladder by binding with a partner nucleotide. As a general rule, adenosine binds with taurine, and cysteine binds with guanine. A goes to T and C goes to G. This is important because, by keeping to this rule, a cell can use single stranded DNA as a sort of photo negative, and use it to make the opposite strand over and over again as many times as it’s needed.

The other “tubes” come in two flavors: microtubules and actin fibers. Microtubules are the scaffolding and road system of an animal cell, keeping thing in place and providing a network of connections to every organelle. Actin fibers are similar to microtubules, except they are more temporary. They are used a lot in things like amoebas to form psuedopods and move around.

Finally there are the actual proteins that make up the molecular motor. Kinesins and myosins are perhaps the neatest looking proteins. They look like thin cartoon characters with really large feet. What they do is they carry or pull things along a tube (a microtubule for kinesins and actin fibers for myosins)by “walking” along it. You can see movies of this like the one below. The feet start out latched to a tube. Then one “foot” will release and latch on again a little ahead of where it was before. Then the other foot will to the same and so on so that the molecule is walking along the tube while carrying some cargo.

DNA polymerase is another molecular motor, though it’s often classified as an enzyme. It latches on to a single strand of DNA, takes phosphates of nearby nucleotides and then uses the energy from the phosphates to attach the nucleotide to its partner on the DNA. If the nucleotide is the wrong match, it gets thrown out. DNA polymerase is basically like a factory worker on an assembly line.

But it’s just a protein.

We’re talking atoms bound together, people. And yet they’re doing these sophisticated things. Perhaps its time we recognized our protein overlords.

Incidentally, if you are interested in this, you might want check out this blog as well: http://informedworship.blogspot.com/

Garage Sale-ing

My family and I have developed a new past time: Garage sale-ing. Of course other folks have no doubt been doing this for awhile, but its new for us. We look through the local paper to find out where they’re having yard sales and then drive to them and look for things to buy. It’s a lot of fun and sometimes we find some good deals.

I mostly look for books and movies. My mom found some antique silver pieces, and my brother made some good deals on ebay. Recently, I got a videocamera that doesn’t appear to work and a lamp, pictured here to the left. I’m hoping to fix the video camera, or figure out how it works.

As for the lamp, I just thought it looked neat. It didn’t have the lampshade when I got it. I paid a dollar for it.  Pretty cool.

Anyway, it’s fun stuff.

Human Error

Marcus stood on the catwalk looking over the trucks and airplanes as they were being loaded with vaccine. “Ladies and Gentlemen!” He called, his voice echoing from the walls of the hanger. “We are about half an hour from go time, those of you who have finished loading your transport may want to take this time to pray. Whatever you believe in, whether it’s God , the Devil, or your lucky rabbit’s foot, get them on the horn. We need all the help we can get. Good bye, and good luck.”

Marcus wiped the sweat beading on his forehead, turned around and walked toward the stairs, wanting to say more, but knowing there wasn’t more to say. Nothing more to do. It was all up to the drivers, the pilots, the guards.

“A rousing speech, Marcus.” Hamilton’s crisp, English voice sang from behind him. “May ask what you believe?”

Marcus paused at the top of the steps then continued down. “I believe in the human race, Hamilton. I have to spend all my energy just doing that. What’s going on with the air conditioning?”

Hamilton was quiet for second or so before answering. “The repair man says it will be at least another hour before he can fix it. We’ll just have to endure it, I’m afraid.”

Marcus whirled around facing the retired British officer. “I’m not asking for my comfort, damn it! If those crates of vaccine get too warm, they’ll be worthless.” When he saw the older man’s lined and weathered face, though, he calmed himself. “I don’t mean to snap at you. You’ve been a great help to us.“

Hamilton raised a hand to say he didn’t mind. “I’ll ask the man to put a rush on it as soon as we get back inside. Maybe an extra body on the problem would help speed things along.”

Marcus nodded and turned back around to continue down the stairs. Hamilton had provided the hanger for them.  Of course the Air Force probably wouldn’t have problems with the air conditioning. Of course any of the military divisions would have probably operated with much greater efficiency. But aside from the National Guard, all the military branches were preparing for an extraterrestrial onslaught that might never happen.

Marcus walked down the length of the hanger, to the door that led to the office area. He had to wait for several people to exit before he could enter. The hanger wasn’t meant for this much traffic.  One of the people leaving, a young man with a mop of blond hair, noticed Marcus, though, and stopped him. “Sir! They’ve translated some of the Glitch message!”

The news had started calling the aliens Glitches, because that was what they seemed to be at first. The Glitches had started their siege by co-opting all satellite communications with what sounded like a mix of feedback and whale calls. Then, without any warning, people started coming down with what seemed at first like a new strain of flu, only the victims started feeling pins and needles sensations, then complete numbness. They became paralyzed, locked in their bodies, unable to move as their nervous systems were systematically destroyed.

“What are they saying?” Marcus asked.

The kid shook his head, flinging a bead of sweat from his eyebrow to the floor. “They can’t tell for sure. They can only make out three words. Exist, allow, and cannot.”

Marcus nodded slowly. “Thanks, son. Get out there and help load, we’re running out of time in this heat.”

“Yes sir!”

“What do you make of that?” Hamilton asked once they were both inside.

Marcus shook his head. “I’m impressed we were able to get that much. An alien language… Heck we didn’t know it was a language until a few weeks ago. But I don’t know how those words help us.”

Hamilton frowned. “I don’t like it. ‘Allow’ and ‘exist’ should not be in a sentence together. Puts our position in a rather different perspective.” An uncomfortable moment passed as the weight of what Hamilton said settled in both men’s hearts. Hamilton coughed lightly. “I’ll talk to the maintenance man.” He rushed away at a speed that was shocking for a man his age.

Marcus walked to the first desk he came to. A young woman was just hanging up the phone, her face pale despite the temperature of the room. “Are the police giving us an escort or not?” Marcus asked.

She shook her head. “They can’t, sir.”

“What do you mean ‘they can’t?’”

She swallowed. “Sir, it’s never been this hot. The wheels of all the police cruisers…they’ve burst.”

“What?” Marcus didn’t bother waiting for an answer. He bounded to the nearest window and opened the blind. The light blinded him at first, the intense heat hitting him like an oven. When his eyes adjusted, he saw the air rippling over the tarmac, the grass yellowing and smoldering.

Marcus closed the blinds quickly. He turned around, his heart and stomach feeling like they had switched places. “Everyone,” He started, but it was too quiet. Everyone was continuing their work, unaware of how the situation had changed. Cannot allow exist, cannot allow exist….

“EVERYONE!” Marcus yelled, and this time he was heard. “Radio all drivers, loaders, and pilots. No one leaves this hanger!”

Marcus ran in the direction Hamilton had gone, dodging people and furniture until he reached the air conditioning control room. Hamilton just finished making his case when Marcus approach the man he was talking to, a small, rough looking man with a moustache and beady eyes. “Can you get us to a sewer?” Marcus asked.

The man nodded. “Great,” Marcus said, “lead as many people down there as you can and get to the city as soon as possible. The aliens have turned the heat on us.”

“Are you sure about this plan?” Hamilton asked, “Won’t the people panic?”

“Have faith, Hamilton,” Marcus said, his eyes wide as he grabbed the Hamilton’s shoulder, “Have faith.”

1 4 5 6 7