Note (12/2015): Hi there! I'm taking some time off here to focus on other projects for a bit. As of October 2016, those other projects include a science book series for kids titled Things That Make You Go Yuck! -- available at Barnes and Noble, Amazon and (hopefully) a bookstore near you!

Co-author Jenn Dlugos and I are also doing some extremely ridiculous things over at Drinkstorm Studios, including our award-winning webseries, Magicland.

There are also a full 100 posts right here in the archives, and feel free to drop me a line at secondhandscience@gmail.com with comments, suggestions or wacky cold fusion ideas. Cheers!

Laser Capture Microdissection


· Categories: Biology
What I’ve Learned:

Laser capture microdissection: the best use of lasers this side of the Death Star.
“Laser capture microdissection: the best use of lasers this side of the Death Star.”

The problem with biology is, it’s messy.

You can open up some animal or person — well, not you, necessarily, but a surgeon or researcher with explicit permission, which is kind of important — and pluck out something you’re interested in. A tumor that needs diagnosis, say. Or a part of the brain not behaving itself. Maybe a gall bladder, because it’s infected or malignant or the doctor has a really weird Pandora bracelet thing going on.

It’s all well and good to decide what you want to carve out. But that’s where biology goes and gets messy.

Take the tumor example. Tumors don’t ordinarily grow in nice neat little balls inside the body, just waiting to be sliced away and stored in formaldehyde or used in a macabre match of bocce. Instead, they ooze between other tissues. They spread tendrils through organs and hop from one body part to another, like some kind of inner-space kudzu. To cut out the tumor, you’ve got to cut other stuff, too. And it’s not always clear which bits are which until the globs of flesh are sliced thin, slapped on microscope slides and diagnosed by a pathologist.

Even normal tissues have the same problem. Say you’re a brain researcher, because you’re a smart cookie and a Futurama fan and you don’t want to rely on Philip J. Fry to save the universe some day. That’s kind of a weird path to a career choice, but hey, it’s your life. Who am I to judge?

Anyway, you might want to study neurons pulled from the brains of lab mice or rats. But in that same brain sample are cells of other types. Glial cells. Skull cells, if you’re a little careless with the scalpel. Liver cells, if you’re a lot careless. The point is, to identify the neurons — and just the neurons — you’ll probably have to slice the tissue up, make some slides and find them under the microscope.

The question is: then what?

For decades, scientists could go through the procedures above and figure out that this sample over here was thirty percent pure for the cells they wanted, and that sample over there was ninety percent pure. But if they wanted to study those cells — pull out DNA or RNA or proteins and see what made them tick — they had no way to get rid of the contaminating schmutz scattered around them.

That’s where laser capture microdissection, or LCM, comes in. It sounds like something Darth Vader might do to torture information out of a Wookie, but it’s not. It’s actually more of a way to get rid of blemishes and impurities in a biological sample. Like an Oil of Olay for microscope slides.

So how many scientists does it take to perform a laser capture microdissection? Three, in principle. First, some smart brave person hooks an ultraviolet or infrared laser to the controls of a microscope, so moving the field of view back and forth will burn a line through the sample. Then a very patient careful person stares into the microscope for an hour or two, twisting the controls like an ungodly-expensive Etch-A-Sketch, tracing around the parts of the sample they want to carve out.

Finally, some brilliant crazy person figures out how to get that laser-jigsawed piece off the slide to do more science. Current methods include melting wax and sticking it to the piece (fairly awesome) to using gravity to shake the piece away (more awesome) to something called a laser pressure catapult (ridiculously awesome). This last procedure involves shooting an unfocused laser at the sample, literally punching the cutout into the air with photon force. Which, again: Wookie torture. But no. Science.

So that’s laser capture microdissection. You get just the bits you want, and none of the bits you don’t. And then you can look at just the cells you like, without anything else getting in the way. It’s as easy as Photoshopping George Costanza out of a vacation pic.

Just don’t try it on a Wookie. That would not end well.

Actual Science:
Modern Drug Discovery – Laser-capture microdissection
BitesizeBio – Laser capture microdissection: get it out!
BioCompare – Laser capture microdissection (LCM): the first step in single cell analysis
The Scientist – Laser microdissection systems
Wired – The human brain gets a new map

Image sources: University of Gothenburg (laser capture microdissection), ikdoeict.be (Fry and the brains), Hurtin Bombs (angry Chewy, vengeful Chewy, purr purr purr), Woosk (Costanza photobomb)

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X-Linked Inheritance


· Categories: Biology, Genetics
What I’ve Learned:

X-linked inheritance: sometimes chromosomes aren't X-actly as they should be.
“X-linked inheritance: sometimes chromosomes aren’t X-actly as they should be.”

We humans have a bunch of chromosomes — balled-up tangles of DNA — lying around our cells. Forty-six of them, in fact, in twenty-three pairs. We get one chromosome of each pair comes from our mother and one from our father — though they may smush together and intermingle during the fertilization process.

(That’s the chromosomes, not our parents. They smushed and intermingled right before the fertilization process, obviously. Also, Barry White was probably involved, which you don’t typically find at the chromosomal level.

Most DNA strands are more into Marvin Gaye.)

The last chromosome pair — the “sex chromosomes” — is special. Males get one copy each of an “X” chromosome and a “Y” chromosome. And females double up on “X” chromosomes, leaving out “Y” altogether.

(The chromosomes get those names because under a microscope, they look a little like the alphabet letters.

To whom, I don’t know. Maybe Elmo from Sesame Street is in charge of naming biological structures.)

Put another way, if a fertilized egg gets the “Y” chromosome from the father (and one of the mother’s “X” chromosomes), the child will be male. If it gets the father’s “X” (and a second “X” from the mother), it’ll be female. Genes on these chromosomes will kick in during development, to determine the sex of the child.

(That’s how it works in humans, anyway, and most other mammals. Some animals have different sex chromosomes — like chickens, where hens have ZW and roosters are ZZ. Or grasshoppers, where females get XX and males get one X, nothing else, and are told to suck it up and stop whining.

Or platypuses, which have ten sex chromosomes, because of course they do. Platypuses are freaking weird.)

The XX versus XY choice has consequences down the line. Many genetic traits are “recessive”, meaning if just one of your two chromosomal copies is defective, you’re fine. Only if both are screwy will you have the trait or disease. For genes on, say, chromosome 3 or 12, that’s okay — everyone’s got two copies, so it’s rare to get both mucked up at once.

But X chromosome genes are trickier. Males only get one copy of X — from their mothers, remember, because to even be male, they had to get a Y from their fathers. If a gene on that lonely X chromosome happens to be horked up, they’re out of luck. There’s no backup, no “chromosome on the cloud” or flash-drive file to recover. One X chromosome, one chance to get all of “X-linked inheritance” right.

Sometimes, it doesn’t happen. If a recessive trait is X-linked and the father has a wonky copy, his daughters will all inherit it — but one bad copy doesn’t hurt. They’ll still get a “normal” X from Mom, and hopscotch happily away. If the mother is affected, all her kids have a 50% chance of catching the bad copy — but again, in girls, it’s covered by a healthy X (this time, from Dad). Only the sons, with mother’s lone mangled chromosome, get dinged by recessive X-linked inheritance.

(Daughters can also get the diseases. But it takes both an affected father and mother — and a bit of bad luck — to be so dinged. It’s like the sperm and egg walked a black cat under a ladder or something.

There’s also “dominant” X-linked inheritance, where even a single defective copy of a gene causes a disease. Females are more likely than males to inherit these conditions, but they’re pretty rare. Overall, X-linked torpedoes still sink males more often.)

So what issues can X-linked inheritance cause? Common recessive disorders include hemophilia, color blindness and certain types of muscular dystrophy. And the rarer stuff includes even nastier syndromes and diseases you wouldn’t wish on your worst newly-fertilized enemy.

So however many X’s you happen to have, be happy that the dice of X-linked inheritance probability didn’t roll snake eyes for you. Unless they did, and then curse the cocked-up chromosomes that combined to mark the mutant-X spot. If only you’d been a platypus, this might not have happened.

Something much weirder, probably. But not this.

Actual Science:
Medline Plus – Sex-linked recessive
NCBI – An introduction to genetic analysis / human genetics
Science Primer – X-linked inheritance
NHS UK – X-linked conditions
Wellcome Trust – X-linked diseases

Image sources: Madical School (X-linked inheritance), AllMusic (White ‘n’ Gaye), Aussie Pete II (Elmo [and Norah Jones!] and Y), Try Nerdy (platypus sex [chromosome] appeal)

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Mitochondrial Eve


· Categories: Biology, Genetics
What I’ve Learned:

Mitochondrial Eve: Making DNA from an ooooooold family recipe.
“Mitochondrial Eve: Making DNA from an ooooooold family recipe.”

Imagine your DNA is a brown bag lunch. Your parents packed it with everything you need. A banana, if you like those. PB&J, maybe — unless your particular DNA makes you allergic to peanuts, in which case, I don’t know. Pizza? Fish heads? Who am I, Andrew freaking Zimmern?

The point is, your DNA comes from both your parents, in more or less equal amounts, and it’s stored in each of your body’s cells in something called a nucleus. That’s the bag in this analogy. Or the kick-ass Tardis lunch box, if you prefer.

Anyway, as she often does, your mother left you a little something extra.

But instead of a “love you” note or an extra Twinkie, our moms gave us something else: a bonus stretch of DNA, passed down only from mothers to children. This DNA is housed in a separate subcellular sack called a mitochondrion. Mitochondria do some pretty amazing things, but that’s a whole other bucket of lunches, so let’s stick to the DNA.

Because mitochondrial DNA is passed straight from mother to child, it can be traced back to earlier generations. Variations in DNA occur at a steady rate, and these get passed down, too. By comparing mitochondrial sequences between individuals, scientists can estimate how closely related they are — the more variations they share, the closer they are. If their DNA variations don’t overlap, it indicates they’re swinging on different branches of the old family tree. When a branch diverges enough to represent a unique DNA signature, it’s called a “haplotype” — a pattern of DNA variation shared by all the members of that branch.

Back in the 1980s, scientists tested mitochondrial DNA from more than one hundred people from different populations and found something unexpected: the variations between subjects suggested that they were all related, anthropologically speaking, by a common female ancestor who’d passed her mitochondrial DNA down the line. The research suggested that everyone in the entire human race shares the same great-great-great-lots-and-lots-more-greats grandmother. And we’re all rocking gently-used, slightly-mutated versions of her mitochondrial DNA.

This ancestral individual is technically called our matrilinear most recent common ancestor, or MRCA, but is more informally known as “mitochondrial Eve”; her maternal genetic makeup is represented in all of our DNA. She’s also been described as the “lucky mother”, since she wasn’t the only woman walking around and having babies at the time. Rather, her lineage — including mothers having daughters, since mitochondrial DNA is only passed by mothers, remember — is unbroken through history, while other childbearing ladies of the time had only sons, or no children, or their daughters didn’t produce more daughters down the line.

The idea of mitochondrial Eve shook science to its lunchtime Twinkies, because it implies a couple of things about human history. First, there was a time (or several) when our population must have been very small, maybe on the verge of extinction. For only one woman’s genetic imprint to have survived, rather than many, suggests there weren’t a whole bunch of humans running around the planet already, with haplotypes of their own. Our species went through some rough times, and only one branch of the tree survived.

The DNA also tells us roughly when this mitochondrial Eve existed. Based on the variability between contemporary humans’ DNA and the rate at which DNA glitches occur, mitochondrial Eve probably lived around 100,000 to 150,000 years ago. And since other evidence suggests that early humans didn’t migrate from Africa until about 95,000 years ago, our ur-granny most likely lived there. And cooked up some nice bits of DNA we’re still using today.

(For the record, we can also trace an “ultimate grandpa” via male lineages and the men-only Y chromosome. The “Y-chromosome Adam” may have lived around the same time as, or tens of thousands of years before, mitochondrial Eve. Their DNA’s early paths are completely independent.)

So next time you’re eating a sack lunch, root around in the bottom a little. Not only might you find a nice note — or a delicious snack cake — but you might discover some 100,000-year-old genetic material, courtesy of mitochondrial Eve. DNA appetit.

Actual Science:
io9 – How mitochondrial Eve connected all humanity and rewrote human evolution
How Stuff Works – Are we all descended from a common female ancestor?
LiveScience – Genetic Adam and Eve uncovered
New Scientist – Found: closest link to Eve, our universal ancestor
Nature – Genetic Adam and Eve did not live too far apart in time

Image sources: Alvin’s Enviro Blog (mitochondrial Eve map), Sierra Club (fishy Zimmern), ThinkGeek (Tardis lunchbox), PlanetKris (mitochondrial mom joke)

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Glial Cells


· Categories: Biology
What I’ve Learned:

Glial cells: you're gonna think lightning; you're gonna cogitate thunder!
“Glial cells: you’re gonna think lightning; you’re gonna cogitate thunder!”

We can’t all be the star of the show.

Think about it — sports tournaments don’t nominate Most Valuable Plethora. Only one actor in a movie gets to be the headliner, pretty much by definition. And no matter how smart those “meddling kids” are, it’s still the Scooby Doo show.

(And don’t you forget it, Fred, ya scarf-wearing frat-boy bossypants.)

Still, there’s nothing wrong with working in the background. Playing cheerleader for the star. (But not head cheerleader, of course.) Being the best darn supporting actor you can be. That’s true everywhere in life — even in our own brains. Most people think of their skulls being filled — or mostly filled, in some cases — with neurons, the cells we use to think and add and learn and compose bawdy limericks about buckets.

But that’s not quite true. Actually, our headbones are only half — or mostly-half — full of neurons. The other half are filled with something called glial cells, which are not neurons, but do help the neurons do their various jobs. And sometimes more.

Consider Rocky Balboa.

(I know. Not a name often associated with matters of the brain, for good reason. But stick with me here; I can make this work.)

Rocky was, of course, the star of the Rocky movies. Sure, he’d get his bloodied butt handed to him for a while by Ivan Drago or Mr. T. or that shifty CIA dude from Predator, but then he’d train up, grunt some stuff and punch them stupid. So it’s his name on the marquees.

But he didn’t do it alone. His trainer Mickey was there to help him — keep him on track, give him advice and yell gibberish at him every once in a while.

That’s what the glial cells in the brain do, more or less, for their diva neurons. First, the glial cells provide physical support and structure. You can’t box on a playground; you need a gym. So the glial cells make the gym our neurons work out in.

And some types of glial cells wrap around neurons, leaving something called a “myelin sheath” behind. This is like strapping the gloves and shoes onto a boxer — the myelin makes neurons quicker and more efficient. Real float-like-a-butterfly stuff.

But that’s only the beginning; glial cells also provide nutrients for neurons. I don’t know what kind, exactly — oxygen, probably, and vitamins; maybe a glassful of raw eggs on heavy logic days? That sounds right.

Another thing glial cells are important for is keeping neurons away from each other. Like professional fighters — especially Hollywood movie professional fighters — neurons like to get in each others’ faces. Or synapses, I guess. But the point is, they’ll talk trash at each other — unless the glial cells get in there and keep them apart. Because you’ve got to save all that cerebral violence for the ring. Or the SATs.

And there’s more; glial cells help neurons by keeping out distractions. Like infections, for instance. Or dead cells. Sleazy fight promoters. Talia Shire, maybe; I don’t know who’s banging around in your head. But whatever butts in, the glial cells boot it out, so the stars can shine. Sting like a bee, baby.

And just like Mickey — a former fighter himself — there’s evidence that some glial cells might even do their own mental “boxing” in the form of releasing transmitters, just like neurons. Not bad for a few billion has-beens and some never-weres, eh?

So the next time you’re thinking about thinking, or anything brains do, give a nod to the glial cells. Neurons are great and all, but without their glia, they’d be a bunch of bums. Bums, Rock! Bums!!

Actual Science:
Network Glia – Glial cells
Science Daily – Neurons listen to glial cells
NPR – To make mice smarter, add a few human brain cells
Scientific American – Know your neurons: what is the ratio of glia to neurons in the brain?
KurzweilAI – More than glue: glia cells found to regulate synapses

Image sources: The MedSchool Project (glial cell), Real Truth About Life… (frowny-faced Fred), Robakers (Mickey lightning, Mickey thunder), Monster’s Movie Mayhem (Rocky on top)

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Alu Element


· Categories: Biology, Genetics
What I’ve Learned:

Alu element: The crowd's not boo-ing, they're Aluuuuu-ing.
“Alu element: The crowd’s not boo-ing, they’re Aluuuuu-ing.”

This is one of those times when being a baseball fan can help you learn something about science.

(All the other times either involve knuckleballs or an obscure branch of physics dedicated to explaining what the hell has kept C.C. Sabathia’s pants up for most of his career. So this one is the best, obviously.)

Back in prehistoric times, before most anyone was born probably, people were playing baseball. I’m talking way back, like 1960 or so. It was around that time that major league baseball was invaded by the Alou family. First came Felipe, then his brother Matty — and then his other brother Jesus. And just when you thought there were no more, another Alou family member, Felipe’s kid Moises, joined the league. And Felipe stuck around as a manager, after his playing days were over.

Basically, Alous were everywhere in baseball. You could scarcely swing a dead Louisville Slugger around the majors without thwacking an Alou element. Not that anyone did that, of course. It would be unsportsmanlike.

A similar thing happened long ago in our genomes. Tens of millions of years ago, some furry little ancestral critter hiccuped, mutationally speaking, and produced the first Alu element. These Alu elements are short snippets of DNA that got erroneously copied out of a gene, mangled, and jammed back into the genome. The DNA bits couldn’t hit a curveball or shag fly balls, but they did have one major-league talent:

They could make copies of themselves, which could then set up shop in other spots in the genome.

Just like the Alous, who didn’t enter the league at the same time or always play for the same team, the Alu elements gradually spread themselves around. The species in which they first popped up was an ancestor of a set of mammals called Euarchontoglires, or “supraprimates”; these include, among other beasts, rodents, tree shrews and primates — including humans. That means that all these species — again, including humans — have Alu elements hanging out on their genomic rosters. Lots of them.

It’s like the Alous signed on — and then made clones of themselves, until they were everywhere all over the field. Real Bugs Bunny vs. Gas-House Gorillas stuff. Only with less cigar-chomping lunks, and more transposable DNA elements.

In total, Alu elements make up more than ten percent of the human genome, and there are more than a million of them in every person’s DNA right now. A few thousand of those are unique to humans, but most can be found in other animals, like those shrews and monkeys and such mentioned above. That’s how we know Alu elements jumped into the game a long time ago; all of these species still list Alus on the roster.

Most copies of the Alu elements don’t do much, since they’re located in stretches of DNA between genes. By hopping willy-nilly around the genome, Alu elements do increase our genetic diversity — and recent reports suggest they may help defend against toxins and viruses. The many copies can mutate over time, however, and they can insert into some pretty inconvenient places. These buttinski Alu copies have been linked with diseases from hemophilia to Alzheimer’s to type II diabetes to several types of cancer.

Which is where the parallel with baseball breaks down. So far as I know, no Alous ever scrambled anyone’s DNA, or made opposing pitchers more susceptible to developing cancer. Getting sent down to the minors, maybe. But never cancer.

So the Alous and the Alus have a few things in common. They’ve both been around for nearly forever, and there are a zillion of each, all a little bit different. But one is a family of All-Stars and sluggers, while the other is hitching a ride in our DNA like a pack of self-cloning subnuclear stowaways.

No wonder the Alous are the ones on the baseball cards.

Actual Science:
DNA Learning Center – How Alu jumps
Science Over a Cuppa – Alu transposable elements and the human genome
Phys.org – Jumping genes have essential biological functions
ScienceDaily – Orangutans harbor ancient primate Alu
Northwestern University – The evolution of Alu-mutations – a clever defense

Image sources: Genome News Network (Alu element), Suite / Kevin Schindler (Alous, Alous everywhere), Business Insider (so much Sabathia), HLNTV.com (Gas-House Clone-rillas)

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