Archive for May, 2010

Rapping about evolution, sociality, cheaters and slugs

May 8th, 2010

An interesting article appeared in the NY Times a couple of days ago. I have my doubts about the general appeal of a rap performance about evolutionary biology, but maybe it’s great. Who knows? You can investigate Baba Brinkman’s “The Rap Guide to Evolution” for yourself here and here.

Of particular interest, the article highlights one part of the show:

Dictyostelium is notorious, in some circles, for its strange life-style. Usually, an individual Dictyostelium lives alone as a single cell. But when food is scarce, the single cells come together and form a being known as “the slug”; this crawls off in search of better conditions. When it finds them, the slug develops into a stalked fruiting body, and releases spores. But here’s the mystery: not all members of the slug get to make spores — and thereby contribute to the next generation — so why do they cooperate?

Dictyostelium is an incredibly interesting group of organisms. A genus of usually solitary, single-celled amoebae, members of the group are also facultatively social. Individual Dictyostelium cells spend most of their life on the forest floor, eating bacteria. When bacteria become scarce, and the amoeba cells start to starve, they release chemical pulses that draw individual cells together. Once together, the cells form a mound of cells, all piled on top of each other. And then something amazing happens, the mound starts to crawl (yes, crawl) as one unit, across the forest floor. This slug is now, by any reasonable definition, a multicellular individual.

A beautiful image of a Dictyostelium discoideum slugs (bottom) and stalks with spore masses on top. Photo credit: Owen Gilbert

But that’s not the end of this startling story. After crawling away a bit (and by the bye, these slugs are visible and you can watch them crawl), cells at the leading edge organize themselves into a stalk, a pillar, via which the lagging cells in the slug will eventually ascend. The stalk cells die, and the other cells crawl up the stalk and become a mass of sporulating cells, leaving clonal offspring that might disperse from the impoverished environment more easily because of the (slight) height. (Well, in fact, this particular sequence is not universal. Some species of Dictyostelium do it differently, but the ultimate product, the formation of a slug and stalked spore body, is the same).

The comparison to wasp workers and queens is clear enough, but the comparison to our bodies is even clearer. Dictyostelium is a group with sterile worker cells and reproductive cells, and the group is composed of genetically identical cells ( . . . well, sometimes). We are a group of cells with sterile workers cells (our soma, all of our tissues and body parts) and reproductive cells (our germ, egg and sperm). The only difference (and it’s a big one, admittedly) is that our worker cell caste has differentiated into many subcastes—different sterile cell types and tissues composed of sterile cells—just like the workers of highly social wasps.

So Dictyostelium is sort of like Polistes: it has cycles of solitary and social, and it bridges the gap between completely selfish and altruist. (In fact, some of the most important work on Dictyostelium comes from the lab of two former(-ish) social wasp researchers). Given this, the next time someone tells you there are no transitionary intermediates that reveal major shifts in evolution, you can point them to Dictyostelium.

So the question: Why do Dictyostelium cells seemingly willingly, suicidally sacrifice themselves, forgo reproduction, and form the structure (the tissue) that is the stalk? The same question applies to worker wasps, and the cells in your finger. The beginings of the answer were provided by Darwin, but the mathematical framework wasn’t worked out for just over a century later, by über-famous social wasp researcher Bill Hamilton. Hamilton’s insight was as simple as it was brilliant.

It goes like this. Imagine an individual I will call the actor. The actor has two reproductive choices: She can reproduce directly by having her own offspring (thus leaving her genes and heritable tendencies, including her tendency to reproduce directly), or she can reproduce indirectly by assisting relatives have enough additional offspring such that they compensate for our actor’s sacrifice in direct reproduction. This works because relatives share genes. So, for example, our actor (let’s assume she’s a human now) could have one child, or help a sister have two additional children (over the children her sister would normally have absent our actor’s help). Because our actor and her sister share genes by descent, in each case, the same amount of genes are left by the our actor. If the actor has one child, she leaves half of her genes to the next generation. If the actor helps her sister have two additional offspring—because she’s related to her full sister by half, and thus related to her nieces and nephews by one quarter—then our actor leaves two times one quarter of her genes, or half, the same as if our actor had one child directly.

Some individuals in populations will have heritable tendencies for direct reproduction (the selfish tendency). Others (due to natural variation) will have heritable tendencies for indirect reproduction (essentially, helping, or being a worker, an altruist). Whichever individuals actually reproduce more, leaving more copies of their genes—including their heritable tendencies for either selfish direct reproduction or altruist indirect reproduction . . . whichever tendency happens to leave the most genes to the next generation will become more common, generation after generation. The other tendency will wane. Either tendency could be more successful, and this can change depending on other external, environmental factors. But whatever the context, if being a sterile helper results in more genes’ being shuttled into the next generation, that tendency will evolve. And the same goes for the tendency for direct reproduction. Neither tendency is universally better. Natural selection decides.

In Dictyostelium, this calculus is simplified, because the cells are (often) all clones of one another, so if one cell reproduces directly or by helping a clone reproduce, the reproductive success to each cell is the same. In this context, conflict-free cooperation can much more easily evolve. Of course, I’ve already pointed out in previous blogs that mutation can strike, and change the behavior of a cell, just like in our bodies. When this happens, the happy harmony is disrupted, and the cheater cell might corrupt the system by reproducing wildly, or otherwise refusing to engage the social contract. This happens in Dictyostelium, just as it does in us. All social systems have cheaters, cancer.

The harmony of Dictyostelium can also be disrupted when slugs are composed of genetically different cells, or even (sometimes) different species. When this happens, cells don’t easily sacrifice themselves and become stalk tissue. It’s easy to see why that behavior might not be favored by natural selection. In this context, becoming a sterile worker might mean very little or no indirect reproduction (for example, if the spores are all distant relatives of the stalk cell). If sterility and helping leave no genes indirectly, the behavior washes away over generations. The only tendencies that are left are the selfish: In a mixed group, fight for direct reproduction or perish. So, this generates great conflict, and individual cells in the slug try to position themselves such that they will be in the spore mass.

Because of this kind of conflict, it was long ago predicted that members of social groups should be able to recognize close relatives. Since that prediction—a prediction that derives directly from the mathematical evolutionary framework I describe above—many social creatures have been shown to recognize kin. You might think this kind of conflict (from genetically distinct cells) has little bearing on humans, but it’s exactly the kind of conflict that stem cell transplants can generate. The potential for that conflict is playing itself out in me now. My new cells have kin recognition abilities, and if they aren’t tricked into thinking my body is kin, a significant conflict may erupt.

So now, I’m like a mixed colony of Dictyostelium. Having hopefully exterminated the mutant cheater cancer cells, I now face yet another other social conflict. As time passes, the probability of that conflict rises.

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Patched up comments function

May 6th, 2010

A number of you have emailed me to say that you can’t figure out how to leave a comment. The way it was set up was a bit awkward, I admit.  So first, I tried some stopgap measures a kludge designed to lead the reader to the comments section, but that meant breaking my posts up, and I don’t want to do that (I’ll be removing those links momentarily).

So, I asked my genius baby, Greg—a PHP whiz—for help. In about three minutes he’d figured a way to rewrite the code such that now, when you click on “Add a Comment” at the bottom of a post, it takes you directly to the comment field, whether a comment has previously been left or not. We’ve tested it on Safari, Firefox, Chrome, and IE. All obey.

Sorry for the nubie hiccups.

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Ol’ Cancer

May 6th, 2010

I’ve received a somewhat strong response to my last post, which is great. Keep the comments and email coming. Regarding that post, many have questioned my final comment about sympathy for my cancer. To be sure, I chose that word to be provocative, but I do have sympathy for all life that is marked for extermination (in this case, by my hand). I have sympathy for the forest that is clear-cut, and I have sympathy for the cattle that we grow to kill and eat. Of course these organisms are not trying to kill me, so naturally my sympathy is greater for them. But I don’t think my cancer is trying to kill me either.

Natural selection dictates that those that are more adept at doing whatever allows them to leave more offspring will be more common in future generations. If their reproductive advantage is heritable, then the traits that allowed them to be more numerous will also be more and more common in the population over time. Imagining, again, that our bodies are a colony of cells, or a nest of wasps, or a school of fish, or whatever, then it’s easy to see why slowly reproducing individuals or individuals that don’t reproduce at all will become less and less numerous over time relative to a rapidly reproducing member of the same group. I thought I’d made clear the restricted sense in which I invoked that term, sympathy.

Looking back, perhaps I could’ve been clearer, but that’s the nature of blogging. The arguments are made mostly extemporaneously, a kind of stream of consciousness. The entire work is presented piecemeal, across days, and new entries sometimes only make sense in light of previous posts. Plus my chief editor is on permanent leave. (Actually, Greg helps a lot with editing.) So I will clarify (or retort) a bit. I don’t mean to criticize any who have responded. (We normally live in Vermont, where I think criticism of what others have said is illegal). I’m just reasserting clarifying my view for the enjoyable dialogue.

When I first read some of the objections, the situation reminded me of a conversation I once had with a Physician’s Assistant who was at the time coring a hole in my ileum for bone marrow. During that delightful visit, we had a chat. At one point, I made some comment along the lines of what I’ve been saying here: The cancer cells are just doing their thing, trying to stay alive, like any creature. Stunned, he looked at me at asserted, “But cancer is bad.” I thought about his short sentence for a long time, and given the context of our conversation, he could only have meant one thing: Cancer is morally bad. Now, don’t get me wrong. He wasn’t suggesting that I had cancer because of my moral failings or past-life no-nos (although I’m amazed at how many do believe such things, and will actually tell me about it to my face). He meant that the cancer itself was evil. You know, just like how wolves are evil for eating cute bunnies.

I now get it that some of you thought that I had written the wrong word, intending instead to say empathy. The substance of the post shows my empathy for my cancer, certainly. I just wanted to express something else for the life that I am desperately trying to kill. That life is not evil; I just find myself in conflict with it.

Obviously, I hate (and I mean that word, too) that I have cancer. I often say (usually to poke fun at the bright-siders) that the only thing I’ve learned from cancer is that I don’t want to have it. I want each and every cell destroyed. Why else would I have endured four years of off-and-on therapy, with the last two years’ mostly futile treatments being virtually continuous. Just because I know the cancer cells are not trying to kill me does not mean I will relent in trying, by any means necessary, to kill them. Self-preservation trumps sympathy.

I invite dissent and alternate perspectives. I’m not doing this just to get my ideas out there; I hope to learn something from this blogging experience too. But I did say what I meant. Just because I have some sympathy for my cancer doesn’t mean I want to help it or keep it as a pet. Who didn’t have sympathy and cry for Ol’ Yeller? But that diseased, frothing mongrel still had to die.

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Conflict between the individual and the group

May 5th, 2010

Okay, I know.  I didn’t actually blog again last night.  Sorry for that, but since I’ve been feeling so, so, so much better, I’ve begun to realize just how much work I was laying aside.  I’ve been catching up.

So as a mini-catchup,  I’ll offer this symbol and some thoughts:

Polistes in Thoreau's attic

Polistes in Thoreau's attic

This is a nest of the genus Polistes—from the attic of the home where Henry David Thoreau was born. (Really.  You’ll just have to trust me on this, okay?)  Greg and I visited Walden Pond and toured Concord with expert historian Joseph Wheeler (grandfather of a good friend of ours, and son of the historian Ruth R. Wheeler, author of Concord: Climate for Freedom) just before I was admitted for my stem cell transplant, over seven weeks ago.

My greatest intellectual influences, without a doubt, come from the 1800s.  Marx, Engels, Darwin, Kropotkin, Emerson, Whitman, and of course Thoreau.   Like millions of other American High School students, I was especially influenced by the Transcendentalists.  But unlike some of my other 19th Century influences, the Transcendentalists—and especially Thoreau, I think—were caught in a kind of struggle.  They all wanted to forge a better world, and they all believed in cooperative alliances and effort; many joined communes and similar groups.  But the Transcendentalists were also great advocates of the individual, and the individual spirit.  This is especially true of Thoreau, who famously retreated from society, lived alone for a few years, and even went to jail in solitary protest against slavery.  At the same time, his writings and his message influenced Gandhi and MLK to reshape society through coordinated group action.  Thoreau is like Polistes.

Polistes is a one of the varieties of wasp I discussed in an earlier post, the kind in which groups of females, all able to have offspring, initially fight to become the egg layer and queen of the colony. There is little-to-no physical evidence of division of labor—no obvious anatomical queen and worker castes.  Eventually, the losers in combat settle down, sort of, and become workers.  But the social group is composed of would-be individualists, biding their time for an opportunity to shrug off their worker roll and take the queen’s throne.  It is a group that exhibits cycles of social behavior interrupted by periods of solitary behavior.  Polistes are the Transcendentalists of the wasp world, symbolically bridging the gap between selfish and altruist, individual and group.

This is how I see Thoreau. For humans as individuals, this might be a good, stable state.  For wasps, it’s unclear to me.  For the colony of cells in our bodies, such conflict is decidedly unwelcome—and when it happens, we call it cancer.

But are our individual cells slave to some purely communist totalitarian society?  Why wouldn’t they “prefer” individuality, a notion so decidedly American?  Does our body’s proper functioning demand that our worker cells (that form our kidney’s, lungs, livers, and, of course, blood) be oppressively chained to a social contract that forces them into a single roll (despite having all the genes needed to perform any roll), never allows them to reproduce freely (many are unable to divide after a point, and all are restricted), and then ultimately commit suicide (apoptosis) when the group so decides? What a dystopian nightmare!

So, as strange as it may sound, from a perspective of freedom, and rejoicing in the individual at all levels—ideas that ignited my intellect and set me on a path to activism and my current study so many years ago—I have sympathy for my cancer.  I cannot blame those cells for wanting to be free.

UPDATE:  See this post.

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A clean bill of health

May 4th, 2010

That’s what I got today.  Except for not knowing if the cancer is really gone . . . and my magnesium levels are not back yet, and my C. difficile sample won’t be finished until tomorrow, and my white blood cells were down slightly.  But in general, I’m doing great.  And I have to say, I have more energy than I’ve had since my oh-so-short remission in 2007.  And the water is clean again.

I’ve only got a sec now, but more blogging later today . . ..

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Busy (and greasy) today, hospital visit tomorrow

May 3rd, 2010

I’ve received tons of great feedback from the blog, and I fully intend to keep blogging, hopefully one or two posts per day minimum.

But today I had a lot of work to catch up on (some of which I got done), and the fact that we can’t bathe makes me sleepy, greasy and grumpy . . . and not much in the mood for blogging.  We can’t bathe because a water main ruptured on Saturday, and now the Boston water supply is contaminated with fecal bacteria.  Just the extremely uncommon event I need right now, eh?  As a result, of course drinking tap water is out, which isn’t a big deal.  But showering is also out—too dangerous for me.  So last night I boiled water for hours, slowly filling the tub to take what was ultimately a very unsatisfying bath.  I woke up this morning feeling gross.  And bathing is very important for me in my condition.  Accumulating bacteria is not exactly what I need to be doing right now.  We considered grabbing a hotel in P-town (cheap right now, before peak season), but then we’d have to contend with carpet, and curtains, and any microbiological gifts the previous visitors might’ve left.  So we just stayed put.  Boston water officials are estimating that the water will be potable again tomorrow afternoon.

And to add to the good times, tomorrow I have my weekly hospital appointment.  Walking into a hospital, with all of its multi-drug resistant strains of god knows what is always a bit difficult. Sitting in a crowded waiting room is even more unnerving.  But, in general I actually enjoy meeting with my physician, and our meetings always go quite well.  If my red blood cells, platelets and magnesium are all in good shape, the appointment will be fast.  If not—if I need a blood transfusion, a platelet transfusion, or a magnesium infusion—I’ll be at the hospital all day long tomorrow.

Red blood cell and platelet transfusions are not awful.  I usually break out in hives—likely due to mismatches in subtle details of blood chemistry.  Sometimes this can lead to the development of antibodies, and therefore immune reaction against blood products, but luckily that has not happened to me.  It’s the magnesium that’s so tough.

As I mentioned in an earlier post, I’m taking a drug called tacrolimus to prevent Graft Verus Host Disease—in which my new immune system (correctly) recognizes that my body’s tissue are foreign, and attacks them.  The tacrolimus is part of the chemical milieu that tricks my new immune system into accepting my body’s tissues as self.  It also leaches magnesium out of my body.  I mentioned earlier that I had to take supplements because of my malnutrition, but I didn’t provide details.  A normal daily supply of magnesium is up to 400 milligrams; I was taking six times that for weeks early on, and even then my magnesium was too low.  Very low magnesium means vigorous, uncontrollable shaking, and left for too long, nerve damage (and I already have that from four years of chemo, thank you).  Over time, the kidneys accommodate and stop leaching the magnesium.  But I’m not sure that’s happening to me yet.  If it’s not, I may have to have a magnesium infusion.  The problem with magnesium infusions is that they make me feel like I’m being burned from the inside—and they take hours; one time I was infused for five hours; my physician did not order that torture (a nurse practitioner did, despite my protestations).  And since that lovely experience, my physician has been very good about allowing me to increase my oral doses so I don’t have to endure the infusions, but there is a limit to how much I can take by mouth, as it too causes diarrhea.  Sheesh!

The point is, I might have a quick day tomorrow, or it could be a long, rotten day.  I guess you’ll know which easily enough: If I don’t post, it’ll be because it was a bad day.

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Boo Yankees!

May 1st, 2010

I haven’t read the literature on this myself, but my oncologist tells me the data are strong that taking walks—or just getting up and about—has a significant impact on recovery, especially regarding fatigue.  So, as I’m feeling so much better (being able to eat tends to do that), my partner Greg and I decided to take a walk today.  We just got back.

Now, going out is no small thing.  We have to select a very open place, with few people, not a lot of dirt or dust in the air, and not much wind.  I have to wear a mask and gloves to prevent acquiring an infection.   Sunblock is required on all exposed skin, so as to avoid stimulating my immune system, which might risk Graft Versus Host Disease (more on that later).  For the same reason I have to wear long pants, a long sleeved shirt, and, because I’m bald, a hat.  So, days ago, my handsome, sweet, loving Greg—who, bless his heart, knows nothing about baseball—went to the store and bought me sunblock and a hat . . . a New York Yankees cap.   And we’re living in . . . ahem . . . Boston.

So, we happen to be living across the street from Church Park, the so-called “mother ship” of the Christian Scientists—who, you know, dismiss medicine in favor of laying on of hands, prayer, and dead children. (Don’t get me started.)  Anyway, we walked around their reflecting pool, and by the time we got to the other side, my feet were starting to hurt pretty bad from the neuropathy—which has been much better, but walking really brings it out.  So we headed home.  No one had commented on my hat, and I thought we were going to slide into home plate, safe.  Alas, steps from our door, a group of snarky young men, seeing my hat, said, “He’s wearing that mask so he won’t get contaminated by the Red Sox.  Boo Yankees!”

I just want to point out that I despise the Yankees, and this is not my fault.

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