These posts, tagged “Primer,” are posted for two reasons: 1). to help me get better at teaching non-scientists about science-related topics; and 2). to help non-scientists learn more about things they otherwise would not. So, while I realize most people won’t read these, I’m going to write them anyway, partially for my own benefit, but mostly for yours.
A good portion of my graduate work centered upon how a given cell will die when exposed to a specific toxin. In order to develop therapies to prevent the death of that cell, the means by which a cell dies is important. It’s also important how a cell doesn’t die, as I’ll explain later on.
We’ll keep this somewhat simple, though. There are two (very) basic ways that cells will expire: necrosis and apoptosis. Necrosis involves the destruction of the cell and, frequently, damage to surrounding cells. Essentially, the cell ends up swelling and exploding, allowing the intracellular materials to leave and get into the surrounding tissue. Frequently, necrosis is accompanied by extreme inflammation, causing things like white blood cells/macrophages, the cellular defenders against infections and invaders, to get to that area and try to clean it up. In the process, they end up creating more damage. Think of it like a “Scorched Earth” policy of eradication of a given problem. “Take it out and everything around it to make sure we cleared it up.”
Apoptosis, on the other hand, is thought to be much more controlled. It is a form of “programmed cell death,” meaning that there are mechanisms built into a cell to allow it to fail properly (unlike the United States banking industry…). Effectively, when specific signals are received, the cell begins the process of dismantling itself, chewing up its own proteins, shutting down its processes, and packaging itself up for a clean removal by nearby macrophages. Rather than the “Scorched Earth” means of cleanup, it’s more like putting things in trash bags and putting it out on the curb for the garbage truck to come by and pick them up for you.
Apoptosis is an extremely important process for other things, though. In the early development of an organism, for example, the neural pathways of the brain and spinal cord are set up such that some neurons will make the proper connection and others won’t. Those that make the proper connection with their target are strengthened, while those that don’t receive an apoptotic signal to shut themselves down and make way for other neurons. Cancer, however, is an example of a disorder where the proper apoptotic signals are not received and the cell decides not to shut itself down as prescribed. Instead, it can’t receive or interpret the signals and continue to reproduce themselves. Eventually, it gets to the point where even the “Scorched Earth” means of eradication by inflammation doesn’t work.
So in general, your body would prefer to go the “apoptosis” route over the “necrosis” route, as the latter tends to produce quite a bit more damage to surrounding cells and tissues that your body would have to repair afterwards. Once a cell has started down the path of necrosis, it’s difficult to turn back and save it. Apoptosis, however, can be limited because it is so dependent upon intracellular signals.
This image is only a fraction of what’s actually going on in apoptosis, but does contain some of the basic signalling mechanisms. Each of those little acronyms is a protein, coded for by a gene in your DNA. Some of them are turned on because of a signal sent from outside the cell, while others are turned on when the cell starts doing something it shouldn’t, so it tells itself it needs to shut down and dismantle itself. However, the key point is that there are ways to use inhibitors toward those proteins to slow down the death of cells, if not stop the death entirely. Alternatively, in the case of cancer, some of those signals above aren’t functioning properly, and if you can determine which signal isn’t working, you can try to replace it, or “skip over” it and start the signal further down the line. Think of it as a game of telephone where each of those acronymns above is a person, but “cancer” occurs when one of those people decides not to continue the game of telephone. We could potentially use drugs to “skip over” that person and keep the game going, or to finish the analogy, to keep apoptosis going.
A lot of what I just said, however, is determined by the ability to personalize medicine. There are a battery of tests that people are run through when they are diagnosed with cancer, but right now, only a few types of cancer can be targeted in such a way. Usually, we just go the “Scorched Earth” route, much like your own body does, but instead we use radiation and chemotherapeutics. Eventually, however, once drugs can be personalized to the individual (e.g. figuring out which person along the telephone line isn’t continuing on with the game), then we should be able to target that cancer specifically and shut it down. Unfortunately, each person is different and each cancer is different (i.e. it isn’t the same person stopping the game in everyone’s situation: it’s sometimes someone else). Each cancer has to be checked individually for which signal isn’t working, and that takes lots of time and lots of money.
But science and medicine is getting there. Slowly, but surely.
