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!

Frameshift Mutation


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

Frameshift mutation: be VERY careful with your threesomes.
“Frameshift mutation: be VERY careful with your threesomes.”

Imagine you’re a Subway “sandwich artist”.

(I know, it’s very depressing. I’m sorry. It’ll only take a minute, and I promise you won’t run into that Jared guy. Because, yikes.)

As a sub Salvador Dali — or if you prefer, po’ boy Picasso, grinder Van Gogh or hero Edward Hopper — you follow three steps to create each “munch-sterpiece”:

  1. Slap down the spongy bread.
  2. Lay in the meatlike substance.
  3. Sprinkle various wilted veggies to taste.

That’s the procedure, one two three, into eternity.

(Or until school’s back in for the fall. Or you get fired for having mayo-balloon fights. As one does.)

But what happens when you get the sandwich dance wrong?

A simple screw-up — substituting the bread with cardboard, for instance — would ruin a single sandwich. (Or not. Possibly no one would notice.) Ditto for getting the steps out of order, slapping your meat on your pickles or some such thing.

But what would really throw things into a state of hoagie higgledy-piggledy would be to skip a step (or add an extra), without changing the overall pattern. If you had bread and meat ready, for instance, and momentarily forgot that vegetables existed.

(Hey, this is America. It happens.)

You’d know there’s a third step to the sandwich, so maybe you’d move on to bread and create a bread-meat-bread order. But now you’ve already done the bread step, so even if you remember the veggies — hello, lettuce! — your process is out of sync. Your next sandwich would be meat-veggies-bread, and so would the other subs after it, until you found a way to make an adjustment. Or until the manager fired you, because you’re making sandwiches like a crazy person.

What you’ve just done — apart from the important public service of encouraging people to eat somewhere better than Subway — is called a frameshift. When it happens in a sandwich shop, it gets a little messy. When it happens in your DNA, it’s called a frameshift mutation, and it can be very, very bad.

That’s because of the way that information in DNA gets used to code for proteins, which do most of the important jobs around our cells. Most of the genes in our DNA code for proteins, but the DNA information goes through another form called RNA to make it happen. The RNA gets created directly from the DNA, “word-for-word” as it were. So if a frameshift mutation occurs in the DNA — one missing bit of information, or one extra — it doesn’t make much difference here. The RNA is just a little longer or shorter than it ought to be.

Making RNA into proteins is trickier, though. Here, three bits of RNA information code for individual amino acids, the building blocks of proteins. And just like with the blimpie Botticellis above, if a triad stutters out of frame, everything afterward goes to hell. The wrong protein gets built, shorter or longer and unable to function the way it’s supposed to. It’s basically a Franken-protein, and all because of one little frameshift mutation.

While frameshift mutations are relatively rare, they can have huge consequences thanks to the complete horking-up of proteins they cause. Frameshift mutations can cause conditions ranging from Tay-Sachs disease to Crohn’s disease to cystic fibrosis to cancer, and more. Any of which are significantly worse than not getting lettuce on your footlong Italian.

You can reduce your risk of developing frameshift mutations by staying away from suspected DNA mutagens. Cigarette smoke. Ultraviolet radiation. Possibly, Subway food. So keep those DNA frames in sync and if you forget the veggies, then for heavens sake, start over. Sandwich safety first, kids.

Actual Science:
Penn State University / Microbiology – Frameshift mutations
San Diego State University / Stanley Maloy – Frame-shift mutations
Study.com – Effects of frameshift mutations: definitions and examples
Baylor College of Medicine – Looking for a shift could provide molecular diagnosis in rare disease
GenomeWeb – Exome sequencing uncovers new monogenic form of obesity

Image sources: Slideplayer / From DNA to Protein (frameshift mutation), The Commercial Curmudgeon (Subway sista), Domestic Geeks (frameshifted sandwich), RedBubble (“the only good way this ends” shirt)

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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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DNA Origami


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

DNA origami: when you're done with your genes, fold 'em up.
“DNA origami: when you’re done with your genes, fold ’em up.”

You may be familiar with origami, the ancient Japanese art of paper folding. In modern Western society, origami usually pops up in one of three places:

  • fancy folded paper in art classes I’m not talented enough to get into
  • fancy folded napkins in restaurants I can’t get reservations for
  • fancy folded towels in hotels I can’t afford

Needless to say, I don’t have a lot of origami experience.

However. Clever scientists — who presumably can’t get into swanky hotels or eateries, either — have recently found something else to fold: DNA.

Like its predecessor, DNA origami started mostly as an art project. Biologists knew that the four bases in DNA — represented by the letters A, C, G and T — pair up in a very specific way (A with T and C with G) to form the double helix structure Watson and Crick were all aflutter about back in the 1950s. They also found that certain strings of bases affected the physical shape of the DNA molecule, making bends, kinks and folds in the structure. With a few careful adjustments, they thought, bits of DNA could become their personal nanoscale genetic-coded Lego set.

So they built some stuff. DNA origami isn’t quite a full-on Lego kit — you can’t make a Millennium Falcon or model Taj Mahal out of genetic material, yet — but the early attempts were still pretty impressive. In 2006, a group managed to assemble DNA triangles, smiley faces, tiny maps, banners, snowflakes and more. So if DNA origami wasn’t exactly DNA Lego then, maybe at least it was DNA Play-Doh.

Since then, the technology has advanced a bit further — and scientists aren’t playing around any more. They’ve got CAD (computer-assisted design) software to design their shapes and calculate molecular bend angles. They’ve also ramped up to try some pretty useful applications. Many of these involve using folded-up DNA structures to deliver drugs like cancer treatments directly into malignant cells. Or basically, using DNA origami as nano-teeny FedEx drivers.

(Assuming FedEx drivers are in the habit of delivering poison to disreputable households.

Which maybe they do. But that sounds like more of a UPS thing.)

There’s still more to do with DNA origami, though. By using long strands of sequence along with complementary base-pairing “staple” strands to reshape, twist and build bigger structures, much more may soon be possible. Last fall, researchers built the largest DNA origami structure yet, roughly seven times larger than anything previously designed — and it mostly self-assembles. DNA-based nanocomputers — and even nanorobots — are also in the works, and may be next.

And that’s all great and everything. DNA origami is cool. I just want somebody to teach me how to fold one of those stupid napkin swans.

Actual Science:
Popular Mechanics – How DNA origami creates supermaterials
Wall Street Journal – Gene expression: origami at the molecular level
Phys.org – Researchers use DNA strands to create nanobot computer inside living animal
The Scientist – Giant DNA origami
io9 – Researchers turn DNA into robotic “transformers”

Image sources: DVice (shiny happy smiley DNA faces), FireHOW (swanny towel), DavidGiuffre.com (“Lego Falcon, yeeeeeah!”), CBS News and ProSportStickers (United *Poison* Service driver)

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Polymerase Chain Reaction


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

PCR: Putting polymerase to good use since 1983.
“PCR: Putting polymerase to good use since 1983.”

The polymerase chain reaction, or PCR, is perhaps the most important laboratory technique in modern genetics. And let’s face it — there aren’t a hell of a lot of “olde-time genetics” to compare with. You don’t see prehistoric cave paintings of chromosomes, is all I’m saying.

And while “polymerase chain reaction” is a scary-sounding mouthful, you can break it down with just a little bit of background. So simple, even a cave painter could understand it.

First things first: PCR was invented back in 1983. One PM (PST), a PHD from the PAC-10, high on PCP, was driving his POS down the PCH with his PYT and poof! PCR just popped into his head.

(Of course, that’s not precisely true. Serious science doesn’t work that way.

He was actually on LSD. So… um, yeah.)

Origins aside, here’s how the polymerase chain reaction works. Under normal conditions, DNA is double-stranded — two strings of genomic sequence wound around each other. But like cheap glue, tight leather pants and bad combovers, when DNA gets hot enough, it comes apart at the seams.

In organisms, there’s a class of enzymes that uses one strand of DNA as a template and builds the complementary strand, producing a new double-stranded DNA sequence. These enzymes are called polymerases — the ‘P’ in PCR — and we wouldn’t be here without them.

(For that matter, neither would fish or philodendrons or athlete’s foot fungus. The job polymerases do, synthesizing sequence from DNA templates, is important for copying genes, making proteins and pretty much everything else a growing cell needs. Which is the only kind of cell there is, really.)

The ‘chain reaction’ part of PCR is performing this process over and over in the lab. With a little molecular juggling, scientists can snip out or “prime” most any sequence for PCR, then produce millions upon millions of copies by cycling through heating and copying, heating and copying, until they’ve made all the DNA they need.

See? Polymerase chain reaction, just like it says. Simple. Ish.

The tremendously useful thing about PCR is, it works on just about any snippet of DNA a researcher might get hot and scientifically-horny about. And each cycle doubles the amount of sequence, give or take a kilobase. You can set up a machine in the evening with some barely-there scrap of genetic fluff, and come back in the morning to bucketfuls of DNA to play with.

Well, not actual bucketfuls. Biochemical bucketfuls. Everything’s relative. But it’s plenty.

So what is PCR used for? At this point, pretty much everything that involves DNA. You name it — mutation screening, DNA fingerprinting, tissue typing, genetic mapping, invasive virus and bacteria detection, parental testing, gene sequencing, genetic mapping and more. Basically, when biochemists do anything past making coffee in the lab, it usually includes PCR.

Of course, scientists don’t actually make coffee in the lab.

Not unless they’re on LSD, anyway. So… um, yeah.

Actual Science:
Science Magazine – PCR and cloning
University of Utah – PCR virtual lab
National Center for Biotechnology Information (NCBI) – PCR
NobelPrize.org – The PCR method – a DNA copying machine
Genetic Engineering and Biotechnology News (GEN) – PCR @ 30: the past, the present and the future

Image sources: UFPE (Brasil) Disciplina de Genetica (PCR), John West (combover), Andrew Wittman and A Time for Such a Word (DNA buckets) and The Premature Curmudgeon (Albert Hofmann / LSD science)

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DNA Polymerase


· Categories: Biology
What I’ve Learned:

DNA polymerase: come with me if you want to replicate.
“DNA polymerase: come with me if you want to replicate.”

DNA polymerase is an enzyme present in every living cell. Hay cells, jay cells, even George Takei cells. Oh, my.

In these cells, DNA polymerase has one job — just one job — and it’s both the easiest and hardest job on Earth. Biology textbooks would tell you that job is to “replicate” the cell’s genetic material, reading and copying DNA so when the cell splits, both new cells contain a full set of genes.

And that’s true, in the same way it’s true that Tito Jackson recorded twenty Jackson 5 records. He did — but he had a hell of a lot of help.

It’s the same with DNA polymerase. It plays an important role in replicating DNA, sure, but it’s led to the job site by an entourage of support proteins, propped into place, and prompted for its lines. Each bit (or “base”) of DNA to be copied is a cue, and it’s DNA polymerase’s job to add the right complementary base in response. There are four different kinds of bases, so it only has four lines to remember.

This is why DNA polymerase’s job is the easiest in the world. It’s treated like a star. It gets driven to the set, carried to the stage, and it barely has to study a script. It just reads a cue and delivers the right line, out of four choices. It’s the gig of a lifetime.

Actually, I imagine it’s a lot like Arnold Schwarzenegger’s life these days. He probably does the odd public appearance for pocket change, followed around by a gaggle of handlers. They’d behave like the DNA replication helpers — getting him to the podium, making his hair look nice and prompting him for the appropriate line:

If it’s a Terminator convention, he’ll say: “I’ll be back!”

At a children’s event: “It’s not a tumah!”

At a GOP fundraiser: “I’m the Governator!”

For a crowd of Predator fans worried about Anna: “Get to da choppa!”

So wherever he goes, a flunky whispers into his ear: “Terminator”, “children”, “GOP” or “Anna”. And Arnold gives the proper response.

(Maybe the flunky even shortens it to one-letter codes: T, C, G and A.

Aw, yeah. You biochemical geneticists see what I did there.)

So DNA polymerase’s job is simple — as easy as a T-800 following a four-path if-then logic loop. Which is to say, it’s easy to do once. Even a few times a week, a la the former-Governator.

But there’s the rub. Human DNA polymerase reads and matches a DNA base about fifty times per second.

(E. coli polymerase is even faster, around one thousand matches per second. If you can picture a bacterial Arnold Schwarzenegger, moving at twenty times the speed. Hasta la nightmare, baby.)

That’s why DNA polymerase has the hardest job in the world. Our genomes are three billion bases long, and in rapidly-dividing cells like skin or hair or stomach lining, the replication never stops. One mismatch could create a mutation that kills the cell, or cause out-of-control growth into cancer. (“Then it IS a tumah!”) Yet our DNA polymerases are extremely accurate, mismatching less than once every ten million bases — and they can even correct their occasional mistakes.

Which is good news for us. It’s no big deal if an aging actor accidentally tells a bunch of six-year-olds to “get to da choppa!“. But our inner Ahhhnolds get their lines right — all the time, nearly every time, and without the help of cue cards. That’s why if it bleeds… we can find DNA polymerase inside it.

Actual Science:
How Stuff Works – DNA replication
The Oncologist – The molecular perspective: DNA polymerase
Wiley – DNA replication
Asian Scientist – Demystifying Rule-Defying DNA Polymerases

Image sources: Vanderbilt University (DNA replication), Fanpop / Michael Jackson (Jackson 5), Screening Notes (“Tumah!”), New England Biolabs and TalkBacker (polymerase T-800)

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