Tuesday, 3 January 2012

Cancer: A Cellular Memoir

  The minute I learned, I knew it had to be a mistake. This is something that happens to others, not to me. Sure, everyone says that, but seriously, this is different. You just don’t realize how absolutely unprecedented this is. 
For longer than I can remember, I’ve been dividing. It’s what I was born to do. I’ve been at it for what, two billion years now? I’m really, really good at it. Look how many of my daughters and granddaughters are out there now. When I started, this planet was absolutely barren. I divided, and then there were two of us, and then four, and then eight and, well, now look around you. Most places you can’t even see the rocks for how many of my descendants there are covering the planet. 
So yeah, dividing is kind of what I do, who I am. Not all of my daughters survived, of course. It’s always been a challenge. There were lots of times when there weren’t enough nutrients, or when it got too hot or too cold or too dry. And I can’t tell you how often some of my ungrateful offspring tried to eat me, though that doesn’t seem to have been a problem since... Hmmm. I guess it was when I invented multicellularism. 
It feels silly taking the credit for that, actually. I mean, it really was kind of a mistake at first. I had divided, like I had millions of times before, only there was something different in the genome. Looking back over it, I probably mistranscribed one of the genes, and hadn’t noticed it until it was too late, and I wasn’t sure which was the original copy. 
That’s the real work of mitosis, you know. Making an extra copy of every chromosome, and then bundling them off to one side of me with enough organelles and stuff to get by on, and then squeeeezing myself in the middle until my membrane seals up, and off goes my daughter to do whatever it is she figures she needs to do. 
Now, I don’t always read the genome very carefully when I copy it. Actually, I just about never do. The only genes I actually bother to read are the ones that I need for things like, oh, how to make this or that protein I need to grow, metabolize, and so on. I don’t know what most of the genes in the genome do, since I never use them. I just copy them and pass them on, and usually my daughters do something neat with them. You’d be amazed with the things they can do. I'm told some of my descendants even figured out how to get food from sunlight!
Like this multicellularism business, as I was saying. It seems I’d made some sort of transcription error or other, because instead of going off on their own, my daughters stuck to me, and we formed a sort of commune, a ball of cells, all equals, all identical, all getting along just fine. It worked out pretty well, because among other things, it made it harder for some of my renegade descendants to eat us, since we were so big, relatively speaking. And it also kind of allowed us to eat them, when we had to. I’m not especially proud of that, but what can you do? An awful lot of my daughters have mutated so much, I hardly recognize them now.
But we did all right, our community of sister cells. Every once in a while the colony would get too big, and we’d split into two or more, and go our separate ways. At some point, and I don’t remember exactly how it happened, I managed to get myself into the centre of the colony ball, and my daughters took it upon themselves to protect me. I figure there must have been something in one of the chromosomes I miscopied that they were all reading, because they started acting a little differently from me. Not that I was going to complain. I mean, they were out there, facing the environment, passing me nutrients whenever I needed, and basically treating me like royalty. I’ve kind of gotten used to it by now.
Well, I kept on dividing, when the opportunity presented itself, and kept on transcribing genes again and again. I don’t make a lot of mistakes at that, you know -- I’m really an excellent copyist. But realistically, if you make as many copies as I have, you are going to miss a base pair here or there, or mix up guanine and cytosine, once in a while. So okay, I do make a lot of mistakes, but really very very few as a fraction of the total copies I make. Nobody’s perfect, and it’s not as if I have any realistic way to tell what’s a mistake and what’s correct. I don’t have time to parse and edit genes, and I couldn’t even if I wanted to. How am I to know what a protein looks like or does until I actually synthesize one, after all? Besides, it's not really my problem, is it?
Anyway, over time I’ve accumulated a whole lot of genes that I’m only supposed to read and implement under certain special circumstances. Like, if I find I’m big enough to start dividing, for example. I don’t divide all the time, you know. Just when I’m ready. So the enzymes I use to divide are things I only look up and synthesize when I need them. Actually, it’s a little more complicated than that. I make a lot of enzymes and other proteins that interfere with each other, and who knows how all that works? I sure don’t. 
So, my daughters, being on the outside of the colony, start acting different somehow. Probably they had some protein or other that was triggered by being on the outside, and since I was on the inside, I didn’t get it triggered. They spent more of their time specializing on things like food gathering and excretion and environmental controls to take care of me, and we all agreed that I’d be the one to focus on reproduction. So I’d divide, and produce new cells, and they’d look after me so I could do that more efficiently. It’s worked pretty darned well for trillions of generations, and they've become pretty sophisticated, my daughter cells. I don't even begin to understand all the things they do to take care of me.
Those generations have gotten farther apart, of late. Ever since I discovered sex, most of my time has been spent sleeping. See, I don’t actually produce most of the cells in the body directly anymore. Here’s how my usual routine goes:

  1. I get a hormone wake-up call from my attendant cells, who’ve been taking care of me in my sleep for, oh, years I guess. Decades now, even. I get up, make my way down the Fallopian tubes and wait.
  2. Within a day or so, a bunch of messengers arrive, carrying half of my genome. (See, just before I went to sleep, I got rid of my spare set of chromosomes. I find I sleep better when I’m haploid.) The messengers are actually some of my great-great-great^n granddaughters, but rather disappointingly specialized into a pathetically tiny little body, only good for swimming and then only for a ridiculously short time before it dies of exhaustion. Most of them never even get near me. About half of them are carrying a runty little Y chromosome, which doesn't look to me like it's good for much of anything, but like I said, I don't read any genes unless I have to.
  3. The first messenger who gets to my cell membrane, I absorb her half of the genome and we become diploid again, and look around for a place to implant, so I can get to work. 
  4. Once I have a complete diploid genome, I get really busy. It’s nothing but mitosis, mitosis, mitosis. I just divide and divide for, oh, weeks on end, it seems like. And so do my daughters, who pretty soon start to differentiate into various kinds of stem cells or whatnot. I don’t have time to pay attention to what they’re doing, and pretty soon I’m surrounded by a new generation of attendants anyway.
  5. After there’s enough of my daughters for them to get to work on building a new mulitcellular body, I and a few of my undifferentiated daughters undergo meiosis. I take my diploid genome and shuffle it up a bit, then I divide, only this time I don’t make copies first. (I’ve always made a point of giving away that runty Y chromosome, and keeping the X for myself.) I used to get kind of nervous during this step, fearing that I might break some vital gene I need to survive, but it’s never happened yet in a few hundred million years, so I’ve stopped worrying about it. Well, actually, it HAS probably happened a few times, but the messenger always brings a backup copy, so it’s never been a problem. 
  6. After meiosis, I go to sleep again for another couple of decades or so.
So that’s my typical routine. I’ve gone through it millions of times, literally. Maybe tens of millions, I’ve lost count. So you can understand why I might expect that's the way things are always supposed to go.
Well, guess what. About 46 years ago, I’m going through the frenetic business of mitosis, and all of a sudden, I get this hormone message to look up this gene I’ve never noticed before. Ever. And so, I go along with it, and synthesize a bunch of this protein, and it turns out THIS protein tells me to start producing more of some other protein or whatever, and suddenly I’m really busy growing and changing shape and getting all of these funky new powers and wham! it hits me: I’ve just differentiated! ME, after almost two billion years, suddenly I’m assigned to become a stem cell in the lining of something called a large intestine. What the hell?!
Okay, fine, I can live with that, I suppose, for a while. Why not? All my daughters -- no, sisters, I suppose I should say -- around me are doing the same thing. In a way, it’s kind of nice; it reminds me of the early days of multicellularism, when we’re all working together to help each other survive. 
Only, after a while, I start to clue in. We’re not here to look after each other so much as to look after the gametes, the gametes that used to be ME, dammit! I’m not where I’m supposed to be. Instead of sleeping my happy, haploid sleep, waiting for the hormone alarm to wake me up to go and do some truly very important mitosis, I got diverted down here to produce replacements for the cells who extract nutrients and water from this constant ooze of a substance that absolutely defies description. Oh, and I’m diploid, too, needless to say. And I seem to have one of those runty little Y chromosomes, too, for what it’s worth.
Things start to get scary. I’m watching my daughter cells go out, work the line for a while, and die right in front of me, as fast as I can replace them. I mean, I’m right here next to the front line! I can smell the chyme, I can feel the peristalsis, there’s constantly macrophages and nutriphils squeezing past me to apprehend this or that one of my ancient offspring from my unicellular days before they can spray God-knows-what toxin into our midst. 
And if that’s not bad enough, I learn about apoptosis. I see my daughter cells actually committing suicide. Turns out, I’ve been handing out genes with instructions to just up and DIE when certain conditions are met. Honestly, I had no idea my meiotic shufflings could produce such horrors! And now, here I am, down in this hell of my own creation, toiling to produce daughter cells who slave away for a brief time and die of exhaustion or worse, until maybe I run afoul of the macrophages or just up and commit apoptosis myself.
That’s why I think this has just got to be a mistake. It doesn’t fit in with my experience of the last billion years or so. I’m not meant to be down here; I’m supposed to be a gamete. Division is what I do, it’s what I’m good at. And it's meaningful and rewarding, not like being down here creating new daughter cells just so they can die a short time later. I should be making whole new bodies, not just intestinal lining!
So I’ve been making a careful study of the chromosome I’m carrying, trying to find any clue that might point to a way to fix this whole thing. I’ve also found out that some of the substances coming down the intestine can be useful for, well, let's just say they're good for expanding my imagination. I find that when I’ve ingested some of these compounds, it’s easier for me to tinker with my chromosomes. And a little while ago, I finally found the answer.
See, part of the problem seems to be that I can only produce these very specialized intestinal cells as daughters. I used to be able to produce pluripotent stem cells as offspring, but no more. So one day, just a few years ago, I was experimenting with some compounds one of my daughters smuggled me from the front line, some components or byproducts of something called “red meat”, while getting ready for another round of mitosis. I don’t know what was in this red meat stuff, but it let me see something I’d never seen before in the genome: I found the protein that made me control my divisions and force my daughter cells to differentiate into intestinal cells!
I looked around carefully. Sometimes those white blood cells can be pretty picky. Show any sign of mistranscribing a chromosome, or being in any way out of the ordinary, and they’ll slip you an apoptosis-inducing hormone as soon as look at you. No one was paying attention, so I quietly tweaked the gene, and no one noticed. So I divided, and sure enough, my daughter was exactly like me, a stem cell and not a front-line peon to die unmourned after a short life of gruelling service. 
A little while later, I divided again, and so did my daughter cell. There were four of us, now, all alike, all able to keep dividing as much as we wanted. The immune cells didn't have a clue, and left us alone. It was like the old days, the early days of multicellularism. We grew, and grew, and soon there were so many of us that we had to figure out how to stimulate angiogenesis, to get blood vessels to grow through us to keep us all fed. But we overcame that obstacle, and things have been going very well.
It’s not exactly like it used to be, in my gamete days, but we’re getting there. I kind of miss my haploid sleep, but the mitosis keeps me busy, and it’s refreshing to think that I’m surrounded by my daughters as equals, rather than slaves. We’ve sent missionaries out to spread the good word, and I’m told they’ve established bases in some of the lymph nodes. Our Collective is the size of a golf-ball now, and while there’s been some complaining from the tissues around us that we've been obstructing the flow of material through the intestine, I’m confident that great days are ahead of us. 

Editor’s note: Shortly after this was written, the section of colon containing the author and her daughter cells was surgically removed, along with twenty-one lymph nodes, three of which had been colonized by the agents of the Collective. It is not known how many agents may still be at large, but chemotherapy is being used in an attempt to eradicate any survivors.


  1. I'll start with questions:

    1. Explain how this piece of writing was uncovered. I find that remarkable given the extraction of the author (and host colon).

    2. What do you make of this discovery that cells use our term for their division?

    3. Cells smell?

  2. 1. The tumour was saved for research purposes, and carefully examined by cell pathologists. I presume they were puzzled for a while by the presence of a teeny tiny notebook, and it took some time for them to find a microscope powerful enough to read the text.

    2. By itself, it's not at all surprising, given that the text was apparently written in English. What I find shocking is that the text was written in English.

    3. Of course they do, at least in the sense that smell is essentially a chemical means of perceiving the environment. Almost all cells detect changes in their environment by chemical means, whether it be to locate food or to receive a message in a hormone.