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!

Yersinia Pestis


· Categories: Biology
What I’ve Learned:

Yersinia pestis: A plague on pretty much ALL the houses, really.
“Yersinia pestis: A plague on pretty much ALL the houses, really.”

Science has helped us to cure a few infectious diseases over the years, like smallpox and polio — and measles, if you live far enough away from Jenny McCarthy. But many dangerous diseases remain, and threaten us all in one way or another. Influenza, for instance. Tuberculosis. Adam Sandler movies.

Also on that list is a name you may not recognize, but which has terrorized the earth for thousands — and humans for hundreds — of years: Yersinia pestis.

That may sound like the name of a Bond villain’s girlfriend, or that animated Disney lady with a grudge against spotted dogs. But it’s actually worse. Much worse.

Yersinia pestis is a species of bacteria, and the disease it causes has been called many things through the centuries. The Plague of Justinian in the 6th century AD. The Black Death in late Middle Ages Europe. Then the Great Plague of Seville, the Great Plague of London, the Russian Plague of 1770-72 and the worldwide Third Pandemic, among many others. At any time, the name changes based on where in the body Yersinia pestis makes its home: pneumonic plague in the lungs, septicemic plague in the blood and bubonic plague in lymph nodes.

Today, we just call it “plague”. Maybe we got lazy with the naming in modern times. I blame Twitter.

No one knew exactly what caused all of these outbreaks until 1894, when Pasteur Institute scientist Alexandre Yersin discovered the culprit bacterium during a plague epidemic in Hong Kong. The species was later named after him; that’s where the Yersinia comes from.

(If the pestis part comes from being a “pest”, that seems like a colossal understatement by whomever is naming these things. A housefly is a pest. Rob Schneider is a pest [who apparently lives too close to Jenny McCarthy]. Yersinia pestis has killed tens of millions of people and once wiped out a third of the European population.

It seems like that rates at least a “Yersinia bothersomeis“. I’m just saying.)

As a bothersome-at-least pathogen, Yersinia pestis has been the subject of much study by modern scientists. Genomes of two of the three known subspecies have been fully sequences, and the genes making these bacteria more virulent than closely-related Yersinia species are well understood. The cycles of infection have been studied, as well — from the fleas harboring bacteria that spread the disease among animals via bites, to rodents like rats and prairie dogs that serve as “reservoir hosts” maintaining bacterial populations, to humans — where Yersinia pestis really gets nasty.

In people, the bacteria survive by following the “best defense is a good offense” strategy. Rather than hiding from our immune system cells, Yersinia pestis meets them head-on. It invades white blood cells, and suppresses the body’s ability to mount an immune response. The bacteria can also kill certain immune cells by injecting proteins directly inside that form pores in the outer membrane, so the insides leak out. Even at a subcellular level, Yersinia pestis plagues are horror movie-level gruesome.

As a final insult, the bacteria often set up shop right in lymph nodes, centers of immune system function. You’d think it was enough to spread all over your body and possibly kill you, but no — Yersinia pestis also wants to rub it in your face.

Luckily, modern science also has a fairly good handle on how to treat the plague. Caught early enough, Yersinia pestis infections respond to antibiotics, and research is ongoing using specific bacterial proteins to make a preventative vaccine.

Still, we’re unlikely to wipe Yersinia pestis completely off the map any time soon. Cases are still reported occasionally today, and recent DNA sequencing performed on material from a 20 million year old fossil flea turned up Miocene Era Yersinia pestis sequence. It seems the world has suffered this “pest” for many, many years and probably will for many, many more to come.

Just like Adam Sandler movies. Sigh.

Actual Science:
Biogeekery – Yersinia pestis: the plague
io9 – This fossilized flea could carry an ancestor of the Black Death
ScienceNews – Genetic tweak turned plague bacterium deadly
LiveScience – Bacteria causing Black Death likely extinct, study finds
NIH / NHGRI – The evolutionary mark of Y. pestis and the Black Death

Image sources: IFLScience (Yersinia pestis micrograph), Wired (Sandler, shocked), Mickey News (Cruella, looking cruel), ETrueHollywoodNonsense (a grinning clueless pesky baboon — and also, an orangutan, I think)

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Wild Type


· 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 Encyclopedia – Wild type
University of Miami – Wild type vs. mutant traits
The Scientist – GM mosquito cuts wild-type numbers
UCSC – The 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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Knockout Mouse


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

Knockout mouse: one lab animal that really goes to the mat for science.
“Knockout mouse: one lab animal that really goes to the mat for science.”

The late author Douglas Adams once said a thing about cats:

If you try and take a cat apart to see how it works, the first thing you have on your hands is a nonworking cat.

He was making a point about how living things are extraordinarily complex, even more so than things like alarm clocks and carburetors and the London Bridge — which, while also complex, can in fact be taken apart and reassembled into reasonable working order.

(By people who are not me. I struggle to reassemble a hamburger after I’ve taken the top off to adjust the pickles.)

Note that the esteemed Mr. Adams never said anything about mice.

Since 1989, scientists have been able to produce essentially the non-cat (and mostly un-messy) equivalent of what Douglas Adams described: a mouse that’s been taken apart to see how it works — and then put back together, with one of the pieces missing.

Unlike your average neighborhood mechanic or electrician, however, the missing bits of these mice are left out intentionally, to find out what they do. And before visions of Frankenmice or other murine monstrosities skitter through your head, let’s clarify that we’re talking about “pieces” at the genetic level. Nobody’s hacksawing the ears off your favorite Disney rodent.

Well. Not for science, anyway.

The term for one of these genetically-altered mice is “knockout mouse”, which sounds like someone Jessica Rabbit shares an apartment with. Or some remedial schlub you have to fight in Punchout if you get your ass kicked by Glass Joe.

Happily, it’s neither. The “knockout” part of the name refers to the knockout of a specific gene. To create a knockout mouse, scientists recreate the sequence of a mouse gene in the laboratory — but with a fatal flaw. They alter the gene sequence so that it can’t produce the functional protein it normally would. They then introduce this broken gene into stem cells collected from mice.

Because the mucked-with gene is still nearly the same sequence as the normal version, some of the stem cells will integrate the new copy into the same spot in the genome, via a process called homologous recombination. It’s a rare occurrence — the cell’s DNA has to need repair in just the right place, when the engineered gene copy happens to be handy — but researchers have designed ways to know when it happens, and to retrieve those few cells where the gene has nestled in just right.

Since each cell contains two sets of chromosomes, the engineered stem cells have one “good” copy of the target gene, in addition to the scrambled one they’ve just picked up. Those stem cells get inserted into an early-stage mouse embryo, which is then implanted into a female mouse to grow. If all goes well, the embryo grows into a baby mouse containing cells from both the original embryo and the injected-in cells. This is called a chimera. And if all goes really well, the sex organs on those baby chimeric mice will come from the injected cells, with one wonky copy of the target gene.

From there, it’s just a hop, skip and a few tiny Barry White albums to a knockout mouse. The chimeras with one wonky copy of the gene in their sperm or eggs are bred, and some of their offspring will inherit that wonky gene — along with a normal copy from the other parent. But, cross-breed a few of those single-copy mice together, and eventually you’ll come up with a mouse with a non-functional copy inherited from both parents. That’s a critter where the gene essentially doesn’t exist any more — and that’s a knockout mouse.

There are now thousands of different types of knockout mice, each demonstrating the effects a particular gene has — by its absence. Knock out one gene, and the mice without it become more susceptible to cancer. Knock out another, and they lose their hair. Another, and the mice grow huge and chubby.

Scientists use knockout mice because many of their genes are similar to ours, and often function in the same way. It’s not a perfect model, but “knockout people” are generally frowned upon in the medical community, so it’ll have to do. And knockout mouse models have been used to study everything from aging to arthritis to obesity to cancer, so they’re extremely useful as research tools.

They might also, according to Douglas Adams’ books, be hyper-intelligent pan-dimensional beings who’ve set up the Earth as a grand cosmic experiment. And he was pretty spot-on about the cat thing, so it’s worth mulling over.

Actual Science:
NIH/NHGRI – Knockout mice
NobelPrize.org – Gene modification in mice
Nature Scitable – Scientists can analyze gene function by deleting gene sequences
Speaking of Research – Lung cancer immunotherapy, from PD-1 knockout mice to clinical trials
Science Daily – Potential role of leptin in diabetes discovered

Image sources: Science Alert (leptin KO mouse), S M Ong (D.N.A., looking devious), Carton-Online (Mickey, missing something), One Gamer’s Thoughts (Monsieur Joe, mid-taunt)

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Lysosome


· Categories: Biology
What I’ve Learned:

'I'm the lysosome. I solve subcellular problems.'
“I’m the lysosome. I solve subcellular problems.”

Everybody has a mess that needs cleaning up, and you usually know who to call to get it taken care of. If you’re staring at the crumby remnants of your BLT, you call the waiter. If the backseat of your car is dirty, you call an auto detailer.

(Or, if the backseat of your car is really dirty, you call Harvey Keitel.)

And if your cell is getting cluttered full of junk, you call the “cleaner” of the microscopic world: the lysosome.

Lysosomes are basically emergency cleaning supplies that (almost all of) your cells keep around, just in case a mess breaks out. That makes sense. You or I might stash a can of Pledge under the sink, or cram some napkins in the glove box. (And straws. Why so many stupid straws?) If things go sideways, at least you have something on hand to do some cleaning.

Your cells are much more hardcore. Or possibly OCD. The cells’ strategy for mess management is essentially to hoard baggies filled with acid and enzymes. These “baggies”, the lysosomes, have a spicy pH of around 4.8, compared to the rest of the cell, which is typically a bland and neutral 7.2. When the cell encounters something it wants to be rid of — a virus, say, or a broken-down mitochondrion, or its mother-in-law — it dumps it into a lysosome, and lets nature take its course.

Where “nature” refers to the acid and more than fifty different kinds of destructive hydrolytic enzymes. And “take its course” means breaking the mess into its molecular components so hard, even its own mother wouldn’t recognize it.

Like I said, cells are hardcore.

Lysosomes are enclosed by the same sort of lipid membrane that covers the cell itself, and can merge together to make bigger “baggies”, as needed. Overall, lysosomes can vary in size by a factor of about ten. And when it comes to cleaning messes, they don’t discriminate; they’ll take care of anything you throw their way. Phagocytosis — the uptake of microscopic critters? Check. Endocytosis — the accumulation of external large molecules and detritus? No problem. And autophagy — fusing with a failing internal cell component to get rid of it? Clean as a lysosomal whistle.

And like most good cleaners, the only time you really notice lysosomes is when they’re not doing their job. Mutations in one of several key enzyme genes can lead to conditions called lysosomal storage diseases. Where these mutations render the lysosomal genes inactive, those enzymes can’t do their job. Certain materials can’t be broken down, and pretty soon the messes back up and clutter the whole cell. If you’ve ever seen an episode of Hoarders, you know that’s pretty bad.

And if you haven’t, then I’ve just told you it’s pretty bad. So now you know.

But mostly, lysosomes quietly do their thing in the background, like an attentive busboy at a restaurant. Or like Winston Wolfe. You may never see the lysosomes in action. But you’ll know when they’ve been there. Because everything will be so clean.

Actual Science:
The Almighty Cell – Lysosome
KUMC Cell and Tissue Biology – Introduction to lysosomes
NTSAD – Lysosome pathology
ScienceDaily – Detecting lysosomal pH with better fluorescent probes
YaleNews – Failure of cells’ ‘garbage disposal’ system may contribute to Alzheimer’s

Image sources: Molecular Expressions (lysosome), Miramax (the Wolf), My Blissful Space (straws in the glove box, yo), Psychology Today (hoarder’s hovel, needs a shovel)

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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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