What’s Cancer?

There’s a nice laymen’s explanation for how most types of diseases work. Viruses, for example, are little pods that inject DNA or RNA into your cells, thus replicating themselves. (Here’s an awesome video by Robert Krulwich and David Bolinsky illustrating how a flu virus works.) Similarly, bacteria, fungi, and various other parasites are independent organisms–made of cells just like us–and its their process of going about their lives inside of us–eating various things (sometimes parts of us), excreting, releasing various chemicals, etc–that makes us sick (or gives us rashes or helps us digest food or boosts our immune system, etc). These various pathogens have evolved to kill. Autoimmune diseases are incredibly complicated (and often poorly understood), but the rough idea is clear: We have cells in our body that are designed to kill off viruses, bacteria, fungi, etc., and sometimes they screw up and kill the good guys instead of the bad guys.

All of those simplified descriptions make perfect sense, and as I’ve become more of a medical nerd, they’ve essentially held up to scrutiny. In other words, they’re good models.

However, the pop-culture description(s) of cancer never really satisfied me. In fact, I would argue that most descriptions of cancer actually ignore the basic question of what the hell this thing is and why it exists. Even my beloved Wikipedia neglects to just come out and say what the damn thing is in its main article about it, though its article on carcinogenesis is pretty good. That type of thing gets on my nerves–I don’t really understand how people can be comfortable talking about something without knowing what it is.

So, until recently, I knew embarrassingly little about cancer. Obviously, I understood that cells mutated and divided rapidly to form cancer, but what made them do that? And why are such a huge variety of things implicated in causing cancer? Radiation, cigarette smoke, HPV, and asbestos are very different things, so how can they all cause the same type of disease? What makes these evil mutant cells so damn deadly? What the hell is metastasis, and why does it happen? I did a decent amount of research and learned some stuff, but I still didn’t really understand what cancer actually is.

That changed thanks to the awesome NPR radio show/podcast Radiolab (which you should absolutely check out if you haven’t already–especially the archives). Their episode on cancer, “Famous Tumors,”finally provided me with a description of cancer that made any sense. It’s still the only decent layman’s explanation of what cancer actually is that I’ve been able to find (and I did a lot of searching while I was writing this blog post up). Once I understood the basics, I found that my other research on the subject actually made sense–even though almost all of it neglected to define the concept in question.

Anyway, you should probably just listen to “Famous Tumors” right now. Seriously. The part that led to my epiphany is a very brief segment that starts around minute eleven or so, and (as is Radiolab’s style), it’s described quite beautifully.

However, for those of you who’d rather read my ramblings, I’ll provide my own description below. In keeping with my tradition of verbosity, this post will take a while to actually mention cancer directly, but I swear the whole thing’s about cancer. Bear with me.

The story starts with a description of what we are:


Evolution and Life as a Cell in a Multicellular Organism

Evolution is a really powerful thing. The human body is by far the most complicated machine that we’ve ever encountered. Indeed, your body is an intricate structure composed of roughly 100 trillion cells. Each of these cells is itself a highly complicated machine–each more intricate than anything man has created. (I discussed this much more in an old post on my other blog.) And, somehow, this system–your body–was developed from nothing by about three billion years of unguided, accidental trial-and-error.

All 100 trillion cells all descended from one cell that existed for a brief period after you were conceived. In some sense, that cell is the fundamental unit of human evolution. That one cell, a funny-looking ball about the size of a period, was you. It promptly divided; the resulting cells then divided, and so on. (If the cells all divided at the same rate and none died, it would only take about forty divisions to create your entire body. Of course, that’s not actually what happens, and that observation is sort of an unjustifiable insult to the number 100 trillion.) Via mechanisms that are still not yet really understood, these cells change as they divide, filling various niches in your body–building nerves and bones and blood vessels and a kidney or two.

(Just to be clear, you don’t understand any of that. You cannot possibly comprehend what it means to be made up of 100 trillion cells, nor what it means for all of you to have once been a sphere less than a millimeter in diameter. Frankly, you probably don’t even really believe that you have kidneys–I certainly don’t–let alone that your kidneys are composed of billions of cells, each with tens of thousands of ribosomes, thousands of mitochondria, a few very long molecules that in some sense define you, etc. But, talking about things that we know are true but will never really understand or truly believe is pretty fun in my opinion.)

What these cells do is really quite reminiscent of the evolution that created you in the first place. As you develop, the cells in your body divide and change. Some of them die. The end result is a bunch of cells that are each well-suited for their specific purposes. Similarly, life evolves by dividing (or reproducing), changing, and dying, leaving the most fit organisms behind on average. But, there’s one incredibly important difference that makes this similarity quite misleading: Individual organisms compete with each other, while your cells are all acting in unison for your benefit–for the benefit of that original cell. Many of them aren’t even that “fit” in the traditional sense.

(Actually, it’s not you or that original cell that they’re working for–even though they are you. The cells in your body are designed–accidentally, but incredibly well–to copy your genes. That’s it. Your body is a giant device that’s designed–again, accidentally–to hold and replicate tiny pieces of a few long, winding molecules. Weird, huh?)

Indeed, your cells make tremendous sacrifices in the name of this greater good. Every day, around fifty billion of your cells actually commit suicide because they have deemed themselves to be more harm than good for your body. They’re even kind enough to do so in a way that makes their remains particularly easy for other cells to digest. And, many specific types of cells go through arguably more extreme sacrifices. In short, your body is a pretty ugly and unforgiving place from a cell’s perspective. (No offense.)

For example, about one quarter of your cells are red blood cells, and RBCs actually extrude their own nuclei as they reach maturity. (It’s hard to find an analogy for this in the macro world–It’s sort of like a self-inflicted combined lobotomy and castration, except worse.) By doing so, they give up the ability to perform almost all cell functions in order to pack as much hemoglobin as tightly as possible. They can’t synthesize proteins once they do this, and since pretty much the only thing cells do is build proteins, they’ve thus basically given up the ability to do anything–They go from being truly alive to essentially being sacks of hemoglobin. Most shockingly, with no nucleus, they can’t divide. (RBCs are instead produced by stem cells in your bone marrow.) So, instead of evolving to live and reproduce, red blood cells actually set themselves up so that they will die rather quickly without being able to reproduce. They anti-evolve.

Of course, I’m choosing evocative wording here. I’m talking about these cells as though they’re individuals with individual needs, and to a large degree, they’re not. You are the organism that evolved to survive and reproduce, not the cells. The cells are part of you, so they’ve evolved simply to keep you alive and to help you reproduce, to work together to protect and replicate your genes. (Thanks, cells!) Your body needs sacks full of hemoglobin floating around in its blood stream to carry oxygen, so your red blood cells turn themselves into sacks of hemoglobin.

Evolution Has Trouble with Semantics

But, survival of the fittest is a fundamental concept. It applies to everything from atoms to molecules to bacteria to humans to stars to galaxies. So, of course, it applies to the cells in your body too. So, what if we think of the individual cells in your body as their own organisms, rather than parts of one large organism?

As I just explained, the cells in your body make a lot of sacrifices for you. In other words, even though they’ve evolved for billions of years, they’re actually not very “fit” at all. (Again, no offense.) Remember the red blood cell that turns itself into a sterile zombie? That’s a really remarkable trick of evolution. In some sense, it’s fighting against itself–struggling to force some cells in your body to behave in ways that violate the basic principle of survival of the fittest.

So, what happens if a cell inside your body ends up not making some of those sacrifices? What if one of your cells started behaving more like an individual, trying to survive and reproduce as best it could?

Well, it would certainly be in a ridiculously hospitable environment, with oxygen and nutrients constantly transported to it, waste promptly carted away, neighbors who don’t compete at all, an immune system to protect it, no predators, etc. It would be the only truly fit cell in a near-ideal world. So, it would of course flourish and reproduce rapidly. Its descendants would do the same, and pretty soon you’d have a big chunk of rapidly growing stuff made up of (roughly) identical cells in your body where it doesn’t belong. That big chunk of stuff is going to compete with other parts of your body for nutrients and space; it might press against things that you probably don’t want pressed against (your trachea or your brain, for example). In other words, it’s going to cause a lot of problems. (More on that later!)

That’s called tumors. It’s a group of cells in your body–a little piece of you–that are no longer towing the line and working for the greater good. It’s evolution fighting against itself–struggling with the definition of an organism. You think of yourself as a single entity; the tumor cells inside you (and, incidentally, there are tumors inside you right now; it’s probably not a big deal, though) is part of you that behaves largely like a separate organism. They’ve mutated from insanely subservient machines into selfish creatures, and once that mutation happens, natural selection runs rampant, because it turns out that life’s pretty good for cells that don’t tow the line.

Indeed, this type of parasite has an amazing advantage over all the other parasites competing for space in your body: It actually is you. It has evolved to live inside your body, just like the rest of you. And, it has the perfect disguise–Lots of parasites try to fool your into thinking that they’re your own cells; cancer cells actually are. So, for the most part, your immune system ignores cancer, and your circulatory kindly nourishes it and cleans up after it.

(Or maybe cancer isn’t part of you? Is something part of you if it no longer abides by the general multicellular principle of one for all? Cancer is a semantic nightmare.)

Cancer’s Arsenal

Just that is terrifying enough, but just how good cancer gets at living and reproducing inside of you is frighteningly remarkable. There are the obvious mutations that make this possible (I’m roughly following Douglas Hanahan and Robert Weinberg’s work here): Most cells basically only grow and multiply when your body asks them to–Cancer cells just grow regardless, and they and keep doing so even when your body says no. They don’t commit suicide, nor do they stop reproducing when they get old. Of course, how cancer actually pulls this off is incredibly nuanced and complicated, but the rough idea is clear: Cancer cells grow, survive, and reproduce a lot more than your body would like.

In addition to these necessary mutations, most cancers also lose most of the body’s natural defenses against further mutation. (Your body wants heart cells where your heart is, for example, so your heart cells have various ways of checking to make sure that their DNA looks about right.) Otherwise, it would be very unlikely that they acquired all of these abilities in the first place.

So, cancer cells typically divide really quickly, rarely stop dividing, and have a greatly increased chance of mutation on each division. As a result, they mutate a lot. This leads to hyper-evolution, and it allows cancers to develop amazing (and extremely frightening) traits. I’ll list them in roughly the order in which they tend to develop:

First, cancer tricks your body into growing blood vessels–lots of them. As I mentioned earlier, your circulatory system nourishes and cleans up after your cancer just like the rest of you. There’s no fundamental difference between a healthy cell taking food and oxygen from and dumping waste into some nearby blood vessel and a cancer cell doing the same. But, any respectable cancer is going to grow into places where cells don’t belong–That’s a big part of what makes cancer so deadly. Your body, of course, does not have blood vessels set up to support not-yet-existent cells in places where it doesn’t want them. So, cancer tricks your body into growing new ones. Your body has a natural and healthy process for constructing new blood vessels, for use when you grow, gain weight, heal from an injury, etc. Cancers evolve the ability to secrete the hormones that start this process. So, your body–the healthy cells in your body–actually constructs the network of blood vessels that cancer uses to survive and grow. Tumors that don’t evolve this ability have to stay within a few millimeters of existing blood vessels, so they typically can’t get too big.

(The extent to which cancer conscripts other healthy cells–various immune cells, endothelial progenitor cells, fibroblasts, etc–is an active area of research.)

Second, cancer actively attacks its surroundings. It actually spews out chemicals that breaks down the various proteins around it. (Radiolab described this as “spewing acid,” but I’m not sure that these chemicals actually count as an acid.) In other words, it quite literally bores holes through its surroundings–through you–to make more room for itself. So, cancer’s not just this cluster of cells that clumsily grows and pushes up against the rest of the cells in your body–It uses targeted, active chemicals to destroy whatever’s in its way. A tumor that has evolved this ability is called “malignant” or “invasive.” (One that hasn’t is “benign,” though this terminology seems to underplay the risk that a benign tumor becomes malignant.) That’s typically when doctors start calling it cancer, as opposed to just a tumor.

Third, cancer swims in your blood (and/or lymph). So, thus far we have a rapidly growing and mutating cluster of cells full of blood vessels, physically and chemically destroying their surroundings. As these cells are chaotically boring through everything in their immediate vicinity, they naturally break their way into a blood vessel or two. This typically doesn’t work out so well; most cells in your body won’t survive in the bloodstream, and cancer cells are no exception. (Lung cancer, for example, is more or less just a bunch of lung cells. Lung cells aren’t made to survive in blood.) But, cancer cells mutate really rapidly, and, at this point, there are typically a lot of them. So, it’s not too unlikely that one of the cells that happens to find itself in a blood vessel will be able to survive. Once that cell gets in and starts dividing, you have cancer in your bloodstream.

Fourth, cancer finds new homes. If you have cancer cells in your bloodstream, dividing, mutating, and spewing chemicals that break down proteins, some are going to get out. As more and more of them get out in different places, mutated in various ways, one of them is going to find a home where it can thrive. Once it starts reproducing, the cancer will have spread–metastasized–to a whole new part of your body. These cells aren’t only cancerous; they’re also just the wrong kind of cell. If you have lung cancer, and it metastasizes in your brain, suddenly you’re growing lung tissue in your brain. That’s not something that you want. Worse still, of course, this is cancerous lung tissue. That’s obviously a big problem.

Why You’re Not Dead

So, obviously, cancer is really terrifying. Perhaps the scariest part about it is just how fundamental this whole process is. It seems inevitable that the cells in your body would evolve–just like you did–to survive and reproduce as much as possible–in other words, more than you’d like.

Of course, the vast majority of your cells do not do this. This is because the cells in your body are designed (accidentally, but really well) to only divide a certain number of times and to avoid mutation. They use a variety of mechanisms to enforce this, including a rigid mechanical limit on the number of divisions, regular suicides, and various DNA repair mechanisms to try to prevent mutations. In order for a cell to evolve into even a benign tumor, it must, at the very least, mutate in an irreparable way, losing both the division limit and its natural tendency to kill itself. Since irreparable mutations that end up having one of these effects are uncommon, the division limit is fairly low (about fifty divisions), and suicides are fairly regular, most cells that mutate in one of these ways either stop dividing or kill themselves before the other mutation takes place. And, these are only two examples of the many mutations that cells must make to even come close to being cancer. All of those mutations have to be irreparable (or, alternatively, the cell line can evolve away the many DNA reparation mechanisms), and they must all happen before any of the not-yet-mutated defense mechanisms ends the cell line’s chance at becoming a tumor. And, of course, at least some of the cells in this mutant cell line have to avoid mutations that would kill them.

But, in spite of that, you do have some tumors in you, unfortunately–right now. A mole, for example, is a tumor, as are many kinds of cysts, like the one currently embedded in my ear lobe… (I don’t want to freak anybody out. It’s a good idea to get your moles checked by a dermatologist, since they are in fact tumors, but obviously don’t freak out and think you’re going to die because you have a mole or a cyst. They’re almost always harmless, as are most tumors.) This is because the number 100 trillion is just so ridiculously huge. The reason that evolution has been able to create such remarkable things is because it’s had so much opportunity to do so–billions of years, and innumerable organisms. 1 Similarly, your body’s 100 trillion cells provide evolution with a great opportunity to run amok, and it does.

But, there’s a big gap between some moles, cysts, and neoplasms and malignant cancer. In the above section, I discussed the obvious mutations that cancers go through–the mutations that make them reproduce and mutate a lot more than normal–and some of the more remarkable ones. The remarkable ones were terrifying, but they’re also a lot less likely to ever happen. And, they’re necessary for a tumor to go from a weird, benign lump to deadly, widespread cancer.

So, you’ve got 100 trillion cells in your body. Some extremely small fraction of them mutate into tumors. Maybe you’ve got between ten and 100 benign tumors in your body–moles and polyps and cysts and things–each made up of ten thousand cells or so. That might sound like a lot of cells, but evolution tends to work on much larger scales.

Plus, the tricks that tumors need to evolve to become malignant are a lot fancier than the few cheap parlor tricks that made the tumor what it is. In general, to go from benign to malignant, a tumor has to start directly competing with the body–evolving ways to fight with it, trick it, go where it doesn’t belong, and survive the body’s countermeasures–instead of just mutating to divide more in various ways. And, the particulars are difficult as well. Tumors that evolve the ability to spew out protein-destroying liquid, for example, might kill themselves in the process.

The only reason that the chance of developing cancer is not completely negligible is the fact that tumor cells are perfect evolutionary candidates–They divide and mutate rapidly, and they live in a very cushy environment. That’s why your doctor might want to remove your mole–even though on its face it might seem sort of absurd to remove just ten thousand cells for fear that one of them might mutate in a particular way.

What You Can Do

You don’t have much control over whether or not you get cancer. The cells in your body are constantly flipping coins, and if one of them happens to get heads fifty-or-so times in a row, you’re going to get malignant cancer. That’s one of the extremely sad burden of being a multicellular organism (but still a small price to pay for the perks, in my opinion).

By far the best thing that you can do to lower your chance of developing cancer is to get screened for tumors. Unfortunately, a lot of the tumors that are easily detectable and removable–like most moles and cysts–aren’t the tumors that tend to turn malignant. But, some are, like tumors in women’s breasts and men’s testicles, so it’s worth checking every once in a while. Plus, it’s not much effort to see a dermatologist occasionally.

And, since cancer originates when one of a very large number of cells does an extremely unlikely thing, it’s a disease whose prevalence can be dramatically altered by extremely small changes. Some carcinogens operate in fairly straightforward ways: Radiation can quite literally smash into your DNA, breaking bonds and changing the molecular structure directly. Cigarette smoke contains a chemical that (turns into another chemical that) can bond directly to DNA and thus mess up the copying process, leading to mutation. (Charred meat contains small amounts of the same chemical, but your gastrointestinal system has a lot of defenses against this problem.) These are called genotoxins, since they more-or-less alter your genes directly. Similarly, some viruses mess with your DNA, and others produce proteins that effectively accomplish the same task.

But, most carcinogens act in extremely subtle ways–making the extremely small chance that a cell becomes cancerous slightly less small–many of which we don’t fully understand. In fact, these effects are so subtle, and we understand them so poorly, that most of the things that we call carcinogens are actually just suspected to be carcinogenic. With no mechanism of action, and no ability to do a controlled study in which we intentionally expose some randomly chosen people to the potential carcinogen, all we can really say is “It looks like people who tend to be exposed to this thing tend to get cancer.” In many of these cases, we’re likely wrong. So, it’s probably not worth much effort to try to avoid carcinogens, except for the extremely well-understood or well-proven ones (e.g., cigarette smoke, asbestos, large doses of radiation).

Anyway, that’s my rant. I hope you enjoyed it. And, seriously, check out Radiolab–They’re awesome.

If you liked this post, you might enjoy my poker blog as well. And, you might want to follow me on Twitter or subscribe to this blog’s RSS feed. I’ve got a lot of posts in the pipeline, so I’ll probably be putting out a decent amount over the next few weeks.

Also, if you liked this post, you might like my post about what color is.

  1. Google did not answer the question of how many organisms have lived on Earth. I actually found a lot of proposed answers that were larger than the number of electrons in the observable universe, which are likely to be false…

7 thoughts on “What’s Cancer?

    1. Noah Stephens-Davidowitz Post author

      Thanks, Zeke. Interesting article.

      Yeah, the computational hurdles facing DNA research are not at all trivial. It’s a bottleneck that people don’t really seem to understand right now, but it’s a really huge problem holding back medical science.

      Some of the tasks required of computers in genomics are quite legitimately hard and still open areas of research. But, as I understand it based on talking to friends who work in the field, there’s also just a lot of instances in which the medical world and the computer science world haven’t properly joined together–i.e. a lot of solutions to problems in computer science haven’t made their way to the medical world. That seems to be changing now, which is a pretty huge deal for people who are interested in the human genome and/or don’t like cancer.

  1. Jacob

    Hey Noah,

    you should read the book “The Emperor of All Maladies: A history of cancer”. It won the pultizer for non-fiction in 2011 and it’s incredibly awesome.

    1. Jacob

      Just kind of skimmed your post, but afaik mammography is only recommended for women that are 50+. Anyway, read the book; it covers shit like this.

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