Spiraling down the double helix

It’s almost mid-month.  I’m at about 19,000 words, about 3,000 words behind my carefully calculated NaNoWriMo goal. (I’ve made an excel spreadsheet). I took my blood pressure yesterday and realized that stressing about keeping up with my self-imposed word count is not helping anything. In fact, my scientific approach to this endeavor – just 2,000 words a day, gives me 5 days off – is totally ludicrous. Creativity doesn’t work like that. I should know better.

Take yesterday. The central theme of my plot involves people researching induced pluripotent stem cells. Informing myself on this seemed the sensible thing to do, so I started reading. Now, I don’t know about you, but it seems to me that the topic of stem cells has been around forever. But did you know that human embryonic stem cells were only discovered in 1998? We’ve only known about these suckers for a dozen years?

One thing led to another. I kept reading article after article, digging myself deeper and deeper into the subject. In 2007, a Japanese researcher, Shinya Yamanaka, found a way to trick adult skin cells into reverting to an embryonic stem cell-like state – basically using trial and error and getting really lucky. That was fantastic news – no need to harvest them from artificially created embryos or aborted fetuses, no need to enter into horrific ethical debates or shady back-room deals buying human oocytes.

Then I wanted to try and understand how they did it: what did they do to the skin cell that took it all the way back to the time of its distant ancestors, to the fleeting moment when it was cozied up in the blastocyst with a bunch of other embryonic stem cells, brim-full of potentiality? Oh, I could be anything, anything at all!

And there’s where I realized that what I know about genetics is basically zilch. And that our DNA is unbelievably, incredibly, magnificently complicated. That’s a lot of adverbs — I know, bad form. But in this case they’re warranted. Really.

Last night, I was talking about it with Marc. Did you know that if you unwound your DNA it would be 2 meters long?

Marc turns over. Don’t be ridiculous.

It’s true!  I insist. I read it on this website…

You shouldn’t believe everything you read on the web, he says, and starts snoring.

Hmmph. I looked it up again this morning. It’s true, if slightly meaningless. If you were somehow to stretch all the DNA in a human cell nucleus out, yes, it would theoretically be 2 meters long. You get that from multiplying the length of a base pair (0.34 nanometers) by a billion (that’s how many base pairs are in the genome). All your cellular DNA would stretch to the moon. Marc’s right in one sense, though – it’s impossible to get your head around an image like that. A vanishingly small sub-microscopic thing that’s two meters long.

It reminds me of the applied math class I took on vorticity in grad school. Imagine an infinite bathtub, the professor said. (He didn’t want to have to deal with boundary conditions). Ummm, excuse me? I say, raising my hand. I’m having a hard time with that…

But it’s helpful all the same when you realize that this implies that DNA is super-tightly coiled up in the nucleus. In humans and other animals, DNA binds to proteins called histones, forming a structure called chromatin. Chromatin is organized into chromosomes – humans have 46 of them. In areas where the chromatin is loosely packed, genes are getting expressed – messenger RNA is transcribing them code and taking it out into the cell to manufacture proteins. Cellular business as usual.

But in other, more densely packed regions, called heterochromatin, the DNA is so tightly wound up that nothing can get in or out. It’s a kind of genetic no-man’s land. If there are genes there, they’re silent. This is where most of the so-called “junk” DNA resides. (that’s another story).

When an embryonic stem cell commits to being a certain kind of cell, there are a bunch of “master regulator” genes that get buried for good in this heterochromatin, never to get transcribed again.

That is, until a Japanese guy unleashes four of them into the cell in the hijacked body of a retrovirus, and then uses some enzyme magic to incorporate them into the gene-expressing part of the genome. Then it’s as if they’d been there all along; they set a whole chain of chemical reactions into motion, taking the skin cell back in time to its embryonic precursor. I can be anything!

Now I’m sure you can see why I’m having such a difficult time meeting my daily word count. I read something, which leads me to ask a question, which I look up and don’t understand, so I try to get a little more background, which makes me realize that there’s another huge gap in my knowledge, so I go try to rectify that situation. Pretty soon it’s midnight and my eyes are bugging out from gazing at the screen too long.

I just spent the last hour unsuccessfully trying to understand gene sequencing techniques.  How do they get the heterochromatin unwound? How they “cut up” the DNA into snippets? How they are able to reconstruct the original chromosome in its entirety in the right order once they’ve sequenced all its base pairs? I haven’t found the answer to any of those questions. Either it’s really complicated or I’m really thick – most likely a combination of the two.

I’m going to have to call a halt to this rapidly accelerating spiral, and get back up to the surface so I can carry on with my story. I’d love to be able to go back in time and be a microbiologist, but I don’t know of any technologies that can take a retrovirus, insert it into my brain cells and reprogram me as a college freshman again. That’s probably a good thing.

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