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 with comments, suggestions or wacky cold fusion ideas. Cheers!

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

Wild type: tame on the outside, tamer on the inside.
“Wild type: tame on the outside, tamer on the inside.”

You would think the term “wild type” would describe the craziest, wackiest, furthest-out-there members of a species. Teen wolves. Mutant carny folk. Donald Trump.

But no.

In genetic terms, “wild type” refers to what you’d find “in the wild”, meaning the usual, most common, textbook examples. The ho-hummers. Been there, seen that.

When biologists describe things as wild type, they’re typically referring to one of two things: genotype or phenotype. The words look and sound nearly the same, but there’s an easy way to keep them straight:

Genotype starts the same way as “gene”, and indeed refers to DNA sequence, where genes live. A wild type genotype is one that matches the sequence most commonly found in the population. So what are you called if you have a different sequence, and your genotype varies from the norm? A mutant.

Not in a bad way, necessarily. But a mutation — either in one of your cells, or in one of your ancestors’ cells which was passed on to you — is how variation gets into genetic sequence, and those variations are tremendously important. Without mutations, we’d all have the same DNA. We’d all be susceptible to the same diseases. We’d have no flexibility as a species to survive. And we’d only have Teenage Ninja Turtles movies. Who the hell would watch those?

(Of course, according to Gattaca, we’d also all look like Jude Law and Uma Thurman. I’m sure there are downsides to that, somehow. I’ll let you know if I think of any.)

Then there’s phenotype, which starts with “phen”, so the easy way to remember that is “it’s not the ‘gene’ one”. Or make up something about “phenomenal”, maybe. Or “phenylalanine”. I don’t know. What am I, your mnemonics coach?

What phenotype refers to is outward appearance or traits. One or more DNA sequence changes (or genotypes) may lead to noticeable physical changes, or phenotypes. In fruit flies, for instance, there’s a gene that controls eye color. Certain genotypic changes, or mutations, in that gene lead to a phenotypic change: instead of beady little red eyes, the flies have beady little white ones.

Not as dramatic a physical change as you get from frappe-ing a fly’s DNA up with Seth Brundle’s, perhaps. But still, a distinctive phenotype — one for wild type, and one for mutants.

In the phenotypic sense, there is no single “wild type”. No one set of characteristics is standard, with offshoots of eye color and skin shade and curliness of hair radiating from it. You can compare variations to each other, but there’s no reference person or animal or bacterium to call ideal.

Likewise, you can come up with a “reference genome” for a species — and people have, for humans and fruit flies and rats and plants and plants and hundreds of other species. But each of these is just an average of the DNA that’s tested. One particular genotypic locus might have a certain sequence in fifty-one percent of the population, so it becomes “wild type”. But everyone else is then a “variant”, and none of us have the same set of millions of variants currently known. We’re all mutants, if you compare our DNA to the human reference genome, though we’re considered wild type in the majority of genomic positions.

Well, most of us are. Not counting Teen Wolf. Or carny folk. Or Trump. The only “wild type” of thing about them is their hair. Their scary mutant hair.

Actual Science:
Science EncyclopediaWild type
University of MiamiWild type vs. mutant traits
The ScientistGM mosquito cuts wild-type numbers
UCSCThe biology of the banana

Image sources: IJMM (wild type vs. mutant sequence), Geek History Lesson (Michael J. Wolf), Junkee (Teenage Wild Type Ninja Turtles), More Than Words (hairpiece with a Trump problem)

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

Gene drives: sometimes CRISPR is the best accessory.
“Gene drives: sometimes CRISPR is the best accessory.”

When you shop for a new outfit, you’re looking for a number of things. It has to fit. It has to look nice. The accessories should match. And ideally, it should be malaria-free.

Genetic scientists don’t shop for clothes much (lab coats never go out of style), but they do struggle with problems like that last one — reducing the impact of diseases around the world. Malaria and others are transmitted via mosquitoes, affecting hundreds of millions of people and killing more than one million worldwide every year. But what if there was a way to genetically alter the blood-sucking little bastards to prevent these infections? And what if it was as easy (relatively speaking, for the lab geek set) as picking out a cute hat to match that kicky new jacket?

Enter the gene drive, which could bring the concept of the extreme makeover to the chromosomes of bugs and pests and maybe even humans all over the world. It works using a system nicknamed CRISPR, which stands for a bunch of long sciency words that no one bothers to remember. The important thing is how it works, which comes below.

(Stick with me here. The beginning doesn’t seem to have much to do with malaria, but it gets better and then all comes together in the end. It’s like the anti-Matrix trilogy.)

Some bacteria have a very clever protein that helps them avoid virus infections. The bacterial cells keep snippets of viral genes around (the structure these are stored in is the thing actually called CRISPR), and this protein — called Cas9 — recognizes the viral sequence as a target, or “guide”. Whenever Cas9 sees this sequence, like when a virus barges in and starts throwing it around the joint, Cas9 cuts it right down the middle and ruins it. No viral genes, no virus, and the bacteria go on to lead long, happy, fulfilling tiny lives. Or not. They’re not really important to the rest of the story, so screw ’em.

The key is, this Cas9 protein doesn’t really care what guide sequence it’s given. So scientists can yank the Cas9 gene out of the bacteria and engineer it into other organisms. Like mosquitoes. They can also engineer in custom guide sequences matching that organism’s DNA — like one for mosquitoes’ immune response to malaria, for instance — and thus effectively delete or mutate just about any gene they like.

With a little extra fiddling — like a perfect scarf that ties the ensemble together — scientists can also use CRISPR and Cas9 to introduce new genes. Better still, those genes can be inserted in particular spots in the genome that have a genetic “competitive advantage”, meaning they get passed on to offspring more readily than most. That means these gene drives could spread through a population faster than the latest French runway fashion. And look damned good doing it.

Gene drives specifically in mosquitoes could be theoretically used in a number of ways. We could make the bugs resistant to malaria and other diseases. We could alter genes that allow insects to pass the disease on. Or we could go all snarky fashion critic on them and wipe them out completely — like skewing their offspring to be nearly all male.

See, “Raining Men” is one thing. But when it rains only men for a few generations, your species got a problem, yo.

The opportunities for gene drives are near-endless. Any species that reproduces sexually — which is most animals, up to and including (most) humans — could theoretically be CRISPR’ed, and convinced to “say yes to the gene”. There are one or two (or thousands) of ethical kinks to work out first, of course. But in terms of the science, we can rebuild those mosquitoes (and nearly everyone else). We have the technology. We can make them less malarial than they were before. Better. Stronger. CRISPRier.

Image sources: Science (mosquito family tree), PRWeb (totally matching accessories), Digital Journal (perfect scarf), Joy Reactor (men, raining [hallelujah])

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

DNA methylation: it's like a chastity belt for your chromosomes.
“DNA methylation: it’s like a chastity belt for your chromosomes.”

We humans have a lot of genes — twenty or thirty thousand, give or take a chromosome. But we also have a problem. All those genes are packed into the DNA of each and every one of our cells. You’ve got genes for hemoglobin next to genes for neurotransmitters next to liver enzyme genes next to the ones that tell your left foot to grow toenails. The whole caboodle, in every single cell.

You can’t have all those genes turned on at once, in all the cells. It’d be a disaster. Think of your DNA as a big walk-in closet full of clothes. Some things go together, some things clash, and other things you only wear for holidays — or when senile-assed Aunt Clara shows up to see the stupid lop-eared bunny suit she bought you. But you don’t wear everything you own all at once. That would make you a crazy person.

So it goes with your cells. Depending on where they live — in a little row house along the spinal column, maybe, or a brownstone in the colon — they want to fit in with the neighbors and express the right set of genes. When in Rome, do as the Romans. And when in the respiratory system, don’t spew out growth hormones. That’s not your job, bunnybutt.

There are several ways that cells can shut down or “silence” genes, but one of the most common is DNA methylation. It sounds complicated, but it’s actually pretty simple. To make a protein in a cell, a bunch of enzymes have to get at the bit of DNA coding for it. Those enzymes read the code into RNA, and the protein is built from that. “Methylation” means taking a methyl group, a single-carbon molecule similar to methane, and glomming it onto that DNA structure like a wad of used chewing gum.

Slap enough methyl groups onto a stretch of DNA, and those RNA-making enzymes can’t get at it. Any genes in the neighborhood get completely shut down, like a Honda running out of gas or a dudebro wearing Axe cologne. Even better, when the cell divides, the DNA methylation pattern gets passed down the line. So it’s a great way for specialized cells to shut off genes they have no business fiddling with — basically a permanent genetic cock block.

Though critical for development in mammals — pssssst, that’s us — DNA methylation isn’t used in the same way by all species. Fruit flies, for instance, apparently have better things to do with most of their DNA, and yeast haughtily looks down its nose at DNA methylation.

Or would, if yeast had a nose. Or eyes. Or the genes for being haughty.

In other organisms, DNA methylation comes up a lot. Some — humans and tomatoes, for two — use it to silence potentially harmful genes inserted by viruses into the genome. DNA methylation tends to decrease over time, so it can be used as an indicator of aging. And it’s been linked to diseases like cancer, Alzheimer’s and atherosclerosis, and could offer clues about how those conditions develop.

So DNA methylation is pretty important. Without it, all our cells would crap out all the possible human proteins and we’d be big unregulated oozing blobs of cytoplasm. Like a certain amorphously-shaped cartoon character with a distinct lack of impulse control.

And that’s not attractive. I don’t care how cute a bunny suit you slap on it.

Image sources: UIUC TCB Group (DNA methylation), The Berry (Ralphie bunny), GenTwenty (dudebro shutdown), UnderScoopFire! (Homer, unregulated)

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

Telomeres in a nutshell: the short of it is bad, and the long of it isn't great, either.
“Telomeres in a nutshell: the short of it is bad, and the long of it isn’t great, either.”

Many things tend to get shorter as we age. Patience. Hairstyles. Time between bathroom breaks.

But something else shortens when we get older, and it’s more important than all the others. Except maybe the haircuts. Nobody likes a geriatric hippie.

This “something else” is a telomere, and it’s a squiggly bit of genetic material stuck on the end of each of our chromosomes, for protection. Sort of like those fiddly plastic things on the ends of shoelaces that stop them from fraying.

(Those are called “aglets”, by the way. That’s not science. I just thought you’d want to know.)

Telomeres play a similar role in our cells — and the cells of most everything else that isn’t a bacterium. When we’re young, the telomeres on the ends of our chromosomes are long. Each time our cells divide, the telomeres get a little shorter, until they’re very small or gone completely. Cells in that state typically don’t divide any more; they’re content to put on a shawl, find a nice rocking chair and wait for the end.

It’s like the aglets on your shoelaces got shorter every time you wore your sneakers, until they finally disintegrated, the laces unraveled and your shoes fell off. Only instead of going barefoot, your hair and skin and brain cells don’t grow back any longer. Which is somewhat more inconvenient, even if you’ve already moved to that shorter hairstyle.

The other more-than-somewhat inconvenient thing about telomere-less chromosomes is that they can lead to cancer. Without those protective bits at the end, genetic material can get chewed away, which is bad. Or chromosomes can link together and loop around, which is also bad. As in, cancer bad. Much worse than frayed shoelaces.

So longer telomeres are better, right? weeeeeell — it depends. In general, yes. Antioxidants in foods like blueberries and kidney beans and artichoke hearts help to lengthen telomeres, and that’s good.

How you get your chromosomes to eat right, I don’t know. Mine are always binging on chips and deoxyribonucleic Oreos.

The thing is, our cells also make an enzyme — called telomerase — that naturally rebuilds telomeres in certain situations. Production of this enzyme is tightly regulated; it’s not normally produced very often or in large quantities. It’s like liquid gold. Or a really good gin and tonic.

In the lab, though, scientists have shown that extending telomeres can reduce signs of aging in mice and worms. Which is great for cowards and lawyers, I suppose — but someday, it could even be applied to humans. That would be sweet.

But there’s a catch. Most of our cells don’t grow constantly. Outside of skin and hair and the insides of our intestines, many cells really shouldn’t be dividing very often. You don’t want lungs the size of life rafts, or a gall bladder you could play volleyball with. Not unless you’re opening a really weird sporting goods store.

So in those cells, if telomerase was always around, the telomeres would keep getting longer. And that might signal the cells that they should divide and divide, out of control. And what are cells dividing willy-nilly, out of control? That’s right: cancer.

So telomeres are tricky. They’re like the Price Is Right showcase game of life: you want as much as you can get, without going over. Because if you do, the consolation prize might be something way worse than Rice-A-Roni.

Image Sources: The Tao of Dana (chromosome telomeres), Heavy (old hippies), Creative Homeschool (aglets), LEXpert (The Price Is Cancer)

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· 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 MagazinePCR and cloning
University of UtahPCR virtual lab
National Center for Biotechnology Information (NCBI)PCR
NobelPrize.orgThe 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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