Genetics for the Rest of Us

April 19, 2011

I work in science. Genetics, specifically, and oncogenomics — or the genetics of cancer — super-duper-specifically. You might think it sounds kind of hard. I always thought that — and figured I’d be shining shoes or giving squeegee jobs for spare change down by the underpass by now.

(Where ‘squeegee job’ is some sort of uncomfortable euphemism. Or maybe it isn’t. Either way, it’s fairly grim.)

I knew that to have any chance in this field — as opposed to living, probably, in a field — that I had to find a way to put science into terms that I could understand. Simple terms. Single-syllable terms. Maybe with finger puppets, or funny hats or something like that barnyard-animal toy that makes noises when you pull the string:

‘The mitotic spindle goes: *OooooWEEEEEOOOOOoooo!!*‘

(I don’t know if that’s true, actually. I’m forty years old and I’ve been married for years. I haven’t heard a mitotic spindle since the Clinton administration.)

“I’m forty years old and I’ve been married for years. I haven’t heard a mitotic spindle since the Clinton administration.”

Anyway, I tried taking science classes in school. Too hard.

So I tried looking up information online, where people talk slower and might animate a GIF or two. Still too hard.

I tried learning from cartoon picture books. That was better; I laughed at some of the pictures. But the words? Too hard.

(Like, Doonesbury hard. I almost blew a cortex trying to ‘get’ one of those strips one Sunday. Beware the long-form ‘thinky’ funny papers, folks.)

I finally decided that if I was ever going to understand any of this nonsense, I’d have to put it in terms that I could understand. Nobody else was going to do it for me — everybody who knew anything about science was too busy engineering intelligent corn stalks or begging the government for grant money or picking out lab coat pocket protectors. They weren’t going to stoop to my level.

(Also, some of them were pretty gangly, or sort of old. Nobody with bad knees should be stooping that low, that long. A major league catcher or world-class reverse limbo-er, maybe.

But a bunch of corn-diddling pocket-protected Professor Frinks? Not so much.)

So I sorted a few things out for myself. And here I am, a few years later, still kicking around in the oncogenomics field. And I barely have to polish any loafers or squeegee any lab coats to keep my position. A couple, around budget time. But otherwise, I’m virtually squeegee-free.

How’d I do it? By breaking just a few basic genetic concepts down into ideas that I could relate to. And in case there are youngsters out there now who are in the same boat I was — no direction, none too bright, goofy haircut — I’d like to share some of those ideas. For inspiration. You can join a field like oncogenomics, if that’s what you want. It just takes a little creative thinking and determination to make it happen.

Also, it doesn’t hurt if you own your own squeegee. But I’m getting ahead of myself. Let’s look at some science:

DNA Base Pairing:

Here’s all you need to know about basic genetics: DNA stands for deoxy-something-that-goes-on-for-six-or-eight-more-syllables-about-something-no-one-ever-remembers. Might as well stand for de-Englished-something-something. Snore.

More practical is this — DNA is made up of four building blocks. These each have names that sound like someone cursing you out in Lebanese.

(Guanine, seriously? Sounds like a slur for someone who’s a little light in their falafels. I’m just saying.)

The rudimentary textbooks — or in my library, all of them — will tell you that the four blocks are represented by the letters A, C, G and T, and that there are specific combinations in which they get together — A always paired with T, and C with G.

Yeah. Too hard.

I prefer to think of our DNA as being made up of beer.

(Which for some of us is perhaps closer to the truth than others. ‘You are what you spill all over your shirt at three in the morning when your motor coordination finally falls to hell,’ as the old saying goes.

Yes, I’m paraphrasing. No, you shut up.)

Once you put these things in beer terms, it all becomes obvious. The Guinness, which is a stout, of course, would naturally want to hang with the delicious extra stout from Coopers Brewery. And the Anchor Steam beer, a light and refreshing brew, would snuggle nicely up to a Tetley’s Bitter. Simple.

Also, it’s obvious that the Tetley’s, from Yorkshire, would never get along with the Irish Guinness. Ditto SanFran’s Anchor Steam and Coopers waaaay over in Australia. It’s a beautiful system.

Even better, you can change it to suit your tastes. More of a Coors or Anheuser-Busch fan? No problem — you’re halfway to DNA already! A few more pints, and you’ll have it all sorted out.

Best of all, with this system homework tends to happen on a bar stool, (re-)convincing yourself that yeah, these two stouts really do taste great together. Or working your way through the ‘T’ beers to complete a set. Or arguing loudly with a bunch of drunken geneticists that if DNA doesn’t have room for ‘V for Victory Hop Devil‘, then to hell with DNA — as soon as you sleep this off, you’re switching over to being a silicon-based life form, that’ll show stupid D-N-A who’s in charge around here, by golly.

You may not pass many molecular biology tests this way. But those nine years of college will just fly by, let me tell you.

Genetic Recombination:

Sometimes, when a man and a women love each other very much, they mingle together their genetic material using techniques that we could only talk about if we were doing this on the Spike Network, after 1am when the kids have all gone to bed. But we’re not, so let’s stick with ‘mingling’.

In the process of this subcellular ugly-bumping, a thing called ‘recombination’ occurs.

(I know, I know — it sounds like something that floppy-hatted engineer from ‘Conjunction Junction’ would warble on about:

“Recombination, what’s that station?

Minglin’ up genes and assortin’ the gametes…”

Don’t worry. It’s not that.

Though when Schoolhouse Rock can’t dumb it down enough to make sense, you know you’ve got some work to do. Moving on.)

Recombination just means that little bits of genetic material fling themselves from one bit of DNA to the other, in somewhat random and unpredictable ways. Which is still too hard. So think of it this way:

Let’s say you’re having a nice romantic dinner with your sweetie. By the time the meal arrives, you’re cooing sweet nothings to each other across the table, leaning in close for meaningful touches and Eskimo kisses.

(Other patrons are asking for retching bags. Could be you, could be salmonella poisoning — you don’t care. You’re in wuv.

This is exactly how it happens in the nucleus, by the way. “Get a room, you two,” growls the endoplasmic reticulum. But no, the chromosomes just keep on spooning. There’s no fighting with horny double helices.)

Now imagine that your meals are made up entirely of salty snacks — hers with Ritz Crackers, maybe, and yours with Chee-tos, or those little mini pretzels you get on the better budget airplanes these days.

(Hey, I said it was ‘romantic’ — I never said you weren’t a cheap-ass tightwad. Maybe you’ll splurge later to split a pack of HoHo’s, eh Romeo?)

And further imagine that you continue to coo and baby talk at each other while you eat your meals. Which leads to a barrage of spitting back and forth, as the crumbs fall and fly and flick where they may.

Now the science. The food is the DNA. The little bits of cracker on your face are from her, and those pretzelly crumbs all up in her eyebrows — nice distance, by the way — are yours. You’ve each got mostly what you ordered, and a little bit of random goop from the other. Congratulations, you’ve recombined. Have a drink of water — and maybe hose off before you split those HoHo’s. There might be young impressionable mitochondria watching.

Mutations and Cancer:

In the academic world of ‘teachyness’, they’d tell you this: DNA is replicated by molecular machinery in the cell nucleus, centered around the DNA polymerase complex. The polymerase has a high fidelity for maintaining proper DNA base pairing, but may introduce a random error in the DNA sequence every ten thousand bases or more. When this happens, the sequence is changed, and — if not repaired — a genetic mutation is the result.

Yeah, that’s great. Also, you lost me at ‘teachyness’.

Here’s my version:

DNA Polymerase — or ‘Pol’ for short — is a lonely guy who scored a job working the door at the sorority house on campus in town, so he’s on his best behavior at all times. Two sets of twins live there, split up in two rooms — Teri bunks with Abby, and Carrie shares a suite with Gabby.

They’re all on young Pol’s radar. I mean, it’s two sets of twins, for crissakes, and he’s a strapping young enzyme and he’s got a subscription to Protein Penthouse Letters. It’s instinct. Don’t judge.)

It’s also his job to check them in — and check them out; how you doin’? — and send them up to the appropriate room before curfew. Meanwhile, he’s a distracted twitchy mess, so while it mostly goes well, it doesn’t always. Mutations are always a possibility.

“Evening, Miss Teri. Go on up to see Abby.”

Good job, Pol. We’ve still got exactly ten fingers, and nothing is webbed. Yet.

“Hi there, Carrie — looking good. Gabby’s already upstairs.”

Awesome. No sickle cell anemia. Nobody ever asked for sickle cell anemia. Nice going, Pol.

“Oh hey, Abby. Go ahead up.”

“I’m Gabby.”

Whoops! If you’re lucky, Gabby’s in a good mood and will shrug it off. That’s what happens most times. Or she’ll be fooled by a quick:

“Yeah, I know. That’s what I said. ‘Gabby’. Gosh!”

But if it’s just the wrong day — maybe she just sat through Genetics 101, say, and is feeling vindictive — then *bam*, she gives you melanoma. Or leukemia, or some nasty brain tumor. Gabby’s kind of a bitch sometimes, frankly.

(Also, Pol, you’re never getting that threesome with any of these four. It’s an all-girls’ school. Do the math, buddy.)

So that’s mutation. And one of the many reasons why I can never work in a sorority house populated only by twins. The chance for genetic disfigurement is simply too high.

Hey, that was fun. Maybe I’ll try this again sometime, with a few more concepts and examples involving the seven dwarves, beer pong, or something horrifically dirty involving Golgi bodies. Maybe all three at once.

(Yeah. Wrap that around your mitotic spindle and smoke it, textbook writers.)

Until then, I’d say, ‘Keep looking at your genes‘. But they’re really small, and you can’t see them without asking one of those lab coat people to help you, and they’d just try to explain what you’re seeing in no-nonsense science-y terms, and where the hell would that get you? Nowhere and a headache, that’s where.

You stick with me, kid. We’ll win a Nobel yet.