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!

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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Mycoplasma


· Categories: Biology
What I’ve Learned:

Mycoplasma: Small things, which probably also come with small packages.
“Mycoplasma: Small things, which probably also come with small packages.”

In every group, there’s one little guy trying to compensate for his small stature by acting tough and being a royal pain in the ass. In the bacterial world, that’s Mycoplasma.

Mycoplasma is a genus — that is, a group of species — of one-celled microscopic critters, just like all other bacteria. But there are a few important differences. For one thing: size. Even by bacterial standards, mycoplasmas are runty; in fact, they hold the record as the smallest living cells known to science.

It’s true. Most people think it’s Verne Troyer. But no. Mycoplasma.

Besides making them cocky and insufferable, mycoplasmas’ small size creates problems for researchers who study them. These bacteria can’t be seen, even under most microscopes, and wriggle through filters that trap their beefier bacterial cousins.

Another difference is the cell wall — a tough layer outside the cell that provides structure and support. Most bacteria (and fungi and algae and plants) have them; mycoplasma species don’t. That’s highly unusual for a single-celled creature. They’re oozing around barely decent, in nothing but their skimpy cell membranes. Mycoplasmas are the creepy exhibitionist neighbors of the bacterial neighborhood, who never put on pants and refuse to close the blinds.

Sadly, the mycoplasmas’ lack of shame causes more problems than the occasional unwanted peepshow. Many antibiotics — including penicillin — attack bacterial cell walls. Mycosplasmas laugh and shake their scantily-clad bacterial butts at these drugs. So if you catch a mycoplasma infection — they cause atypical pneumonia and pelvic inflammatory disease, among others — you won’t get rid of them with the usual antibiotic suspects. The little bastards actually are tougher than they look.

But mycoplasma species aren’t just compensating for puny size. Besides the cell wall, they have genomes smaller than most any other organism — so small, scientists were able to synthesize the whole thing from scratch and effectively create a “synthetic” bacterial cell using the DNA.

Also, they can’t make any of their own amino acids, and leech cholesterol from whatever they’ve infected to shore up their cell membranes. So in a sense, mycoplasmas are incomplete — dependent on hosts to survive, feeble and literally devolving. Scientists think the cell wall and genetic material were lost from Mycoplasma species after they split off from other bacteria.

Seriously, no wonder they’re a pain in the ass. I wouldn’t be surprised if mycoplasmas all had hair plugs and gold chains and drove teeny little BMWs.

Mycoplasmas are so screwy, they’re a big problem for biologists — even the biologists not trying to study them. Maybe especially the ones not trying to study them.

The issue is, mycoplasma contaminations are very hard to detect and require special tests. Much biological research depends on cell lines and tissue cultures — living cells extracted from humans or animals that can be grown in the lab and tested in various ways. But if mycoplasma is lurking unseen inside those cells, then any test results could be compromised. And it’s estimated that a third or more of the world’s cultures may be contaminated.

All that runty bacterial goop screws up the real science, and no one knows exactly what the results are until the cells are cleaned up and experiments repeated. This costs time, money and — worst of all — graduate student sanity. Those poor lackeys don’t have much to begin with, and mycoplasma infections can shred their last remaining wits. I’ve seen it. It’s tragic.

So beware of the Mycosplasma species. They’re tiny, overcompensating, and seemingly everywhere. They’ll make you sick, drive you crazy and get less evolved every day. In short, mycoplasmas are like an unseen horde of Rob Schneiders, storming into your favorite cells. The horror. Oh, the HORROR.

Actual Science:
MicrobeWiki / Kenyon College – Mycoplasma
The Scientist – Out, damned mycoplasma!
Nature – Researchers start up cell with synthetic genome
Journal of the American Medical Association (JAMA) – Newly discovered protein helps mycoplasma evade immune response
MIT Technology Review – Human genome contaminated with mycoplasma DNA

Image sources: Animal Architecture (synthetic mycoplasma), US Magazine (Verne Troyer), AutoWeb (small penis), Suitably Bored and SodaHead (Schneider horde)

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Australopithecus


· Categories: Biology
What I’ve Learned:

Australopithecus: In hominid evolution, you win some, you Lucy some.
“Australopithecus: In hominid evolution, you win some, you Lucy some.”

Australopithecus sounds like an oddball instrument some grimy dreadlocked dude from New Zealand would play — or possibly a disease you might catch from said grimy Kiwi dude, if you stood too close to him during the concert.

Happily, Australopithecus is actually a genus — that is, a group of species — that lived in southern and eastern Africa between about two and four million years ago. The term “Australopithecus” means “southern ape”, which is a reasonable description of these hairy prehistoric hominid furballs.

(Also, it’s probably not a bad description of that nappy New Zealander. I’m just saying.)

The Australopithecus species — including the famous “Lucy” specimen — are particularly interesting, because they’re the earliest fossil remains of ape-like creatures that weren’t particularly ape-like. Though they had relatively small brains, analyses of Australopithecus toes, feet and hips reveal that they could probably walk upright. They may have also played hopscotch and danced the lambada on steamy Saturday nights.

(Those last bits aren’t really supported by the science. I just like to picture them.)

Also, most Australopithecus species have powerful teeth and jaws not seen in apes, and some may have even used tools. So they were no longer true apes; they were more like apes crossed with crocodiles who could walk on two legs and work a can opener, but probably played a lousy game of chess because their brains were still the size of golf balls.

Or, basically a pack of slightly-hairier Rachael Rays. I apologize in advance for the nightmares that phrase will surely cause.

Thus, Australopithecus has answered one important question about human evolution: the adaptation to stand upright was not driven by the development of a big, human-like brain. Early hominids were walking (and cooking 30-minute meals, apparently) before they had the ginormous craniums we’re all so proud of.

But another question remains: were the Australopithecus species, the original bipedal hairballs, direct ancestors of modern-day humans? It depends on who you ask.

(Just don’t ask Rachael Ray. She’s kind of sensitive about it.)

On one hand, there’s good evidence that Australopithecus species walked upright, and they have several features — like particular bone shapes and relative sizes — intermediate between earlier species’ skeletons and those found in doctors’ offices and Halloween costume shops today. Some scientists say: if it mostly waddles like a prehistoric duck, and it vaguely quacks like a prehistoric duck, then slap a mammoth skin on it and call it Daffy. For them, chances are we have Australopithecuses in our family tree.

Other scientists aren’t so sure. “Upright” is one thing, but these pre-humans probably didn’t walk or run like we do, and likely still climbed trees and “knuckle-walked” on a regular basis. Also, there were still Australopithecus species hanging around after the Homo genus emerged about 2.4 million years ago. Did the Homo species, including Homo sapiens — i.e., every human on the planet, except possibly Carrot Top — evolve from one of the earlier Australopithecus groups? Or intermingle with a later one? Did we evolve from a common ancestor, then watch their branch die out over the millennia?

At this point, nobody knows for sure. More fossil specimens — like the new species Australopithecus sediba, described in 2010 — may someday provide conclusive evidence of a link between the genuses. That would be exciting news, indeed.

Except then we’d have to invite Rachael Ray to the family reunions. And nobody wants to be at that potluck, Junior. Pass the prehistoric potato salad.

Actual Science:
Nature – Overview of hominin evolution
Dr. Dennis O’Neil / Palomar College – Analysis of early hominins
LiveScience – Early human ‘Lucy’ swung from the trees
Archaeology – The human mosaic
ScienceDaily – Little Foot is oldest complete Australopithecus, new stratigraphic research shows

Image sources: Discovering Cultures (Australopithecus), Go, See, Write (dreadlocked dude), ResearchMatters/ASU and Armchair Cook (Rachael Ape), After and Before (Make-it-stop, Carrot Top)

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Synthetic Genomics


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

Synthetic genomics: when regular old DNA just won't do.
“Synthetic genomics: when regular old DNA just won’t do.”

Genomics is the study of and the fiddling with (science term) an organism’s DNA. So naturally, you might think that “synthetic genomics” is studying and fiddling with DNA while wearing polyester.

It’s not. From what I’ve seen of most biologists’ wardrobes, the polyester thing is pretty much implied in all of genomics. And most weekend parties.

Instead, synthetic genomics is a particular style of fiddling with DNA that uses components and rules that nature hasn’t gotten around to trying yet.

(Because nature tends to be very busy doing other things. And in her spare time, distracted by all the polyester.)

There’s a big difference between sciences like “genetic modification” or “genetic engineering” and synthetic genomics. All sorts of organisms’ genomes have now been modified in the lab — corn, for instance, and glow-in-the-dark fish, and possibly Jocelyn Wildenstein. But in these cases, the genes engineered into the DNA came from other species in nature, and followed the usual rules for how DNA works.

(Not how faces work, necessarily. But at the DNA level, it’s all textbook. And usually a difference of just one or two genes.)

But synthetic genomics is different. Here, the usual rules go out the window. Recently, a team of scientists used computers to redesign a chromosome found in yeast, synthesized the new sequence and plugged it back into real yeast cells.

Why? I’m not entirely sure. Maybe they’re trying to create glow-in-the-dark beer, or sandwich bread that talks to you while you eat it. Both of which I’m in favor of — preferably in the same meal. But in the meantime, it’s a monumental bioengineering achievement, and could produce more efficient yeast.

No doubt the Pillsbury dough boy and Budweiser Clydesdales are salivating over that.

Another team is trying to modify pig DNA to look more similar to humans. Which, of course, because a real-life Porky Pig is an obvious choice to be the next judge on The Voice. But actually, it’s so pig lungs can be yanked out and transplanted to save humans with terminal lung disease, while eliminating the problem of foreign tissue rejection.

Which just goes to show, everything is better with bacon. Including cross-species thoracic surgery. Mmmmmm, bacon.)

The biggest news to come out of synthetic genomics recently is that the DNA inside every living thing — from bacteria to badgers to Barbara Walters — can be expanded upon. Improved. Turned to eleven.

Announced just this week, scientists at the Scripps Research Institute whipped up a strain of E. coli bacteria that don’t just use the usual four basic building blocks of DNA, but instead use six.

This is big news. It’s like when Columbus turned Europeans on to a whole new continent, or Lewis and Clark followed Sacagawea through the Northwest, or the day you discovered you like actually dark beer. Whole new frontiers open up, full of possibility and hangovers and grizzly bear attacks.

And now, full of semi-synthetic genetically-fiddled-with E. coli., like little microscopic scientists wearing polyester pants. Sometimes the bacteria don’t fall far from the tree.

In practical terms, an expanded DNA alphabet could lead to revolutions in genetics, bioengineering and the ability to mass-produce useful proteins that have never before existed.

Whether that will finally improve biologists’ wardrobes is still up in the air. Science can only do so much.

Actual Science:
EMBO Press – Genome-scale engineering for systems and synthetic biology
Discover – Life as we grow itL the promises and perils of synthetic biology
Nature – First synthetic yeast chromosome revealed
CBC News – Modified pig organs could help late-stage cancer patients
Genetic Engineering and Biotechnology News – Expanded DNA alphabet moves from test tube to life form

Image sources: ChemistryWorld (6-base DNA), NBC New York (Jocelyn Wild-n-woolly-stein), Broadway World and Popscreen (Porky and the Voice), Unstable Molecules (unfashionable scientists [Phil and Lem, awww])

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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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