As I enter the latter years of the PhD portion of my MD/PhD training, I’ve wrestled with how to develop a “mechanistic” set of experiments to explain the autoantibodies I have found in a series of immunodeficiencies. In science, “mechanism” is a loaded word, and I’ve struggled to find it for my project but also struggled to define it.
I’ll start with my definition. “Mechanism” is explaining how something works. I’ll start with a clean example. If you see that you have a rash over your arm and you are wearing a metal bracelet, this is an observation. That could lead you to a hypothesis that the metal in your bracelet causes an allergic reaction on your skin. Your correlative observation that you were wearing a bracelet and developed a rash in the same spot at the same time is in support of this hypothesis, but it doesn’t prove it.
You could then perform a series of experiments, where you wear your bracelet only on Tuesdays for a month. If you observed a rash only on Tuesdays, you would prove that your bracelet does indeed cause an allergic rash on your body. But you can iterate on this finding. You could ask whether the rash-causing factor in the bracelet is nickel or some other metal, and you could repeat the experiment using a nickel-only bracelet.
You can see how there is a process of digging deeper and deeper into science, and this is “mechanism”. Both the beauty and the bane of mechanism is that its depth is infinite. For the bracelet rash phenomenon, you could dig deeper into mechanism by asking whether the rash was histamine dependent. To answer this question, you could repeat the bracelet experiment while taking Benadryl, an over the counter anti-histamine. These experiments could be only the beginning of an extensive line of scientific inquiry.
There is a comedy sketch where the comedian Louis C.K.’s daughter asks him something along the lines of, why they were having macaroni for dinner. In response to his answers, the daughter repeats the question, “Why?” about a dozen times until they arrive at a metaphysical question like why does God exist. Louis C.K. then proceeds to tell her to shut up and eat her dinner. That little girl’s line of questioning is a lot like mechanism.
For any given observation, there is no definitive end point in our understanding, and the point at which you are satisfied with your understanding is remarkably arbitrary. And that is its own set of questions; when are we satisfied with our understanding and what keeps us curious?