that has recurred over evolutionary time where it would have given an advantage?”
Nesse has written extensively about how emotional responses might be shaped by evolution. “All of these different aspects of emotions—physiology, subjective experience, cognition, behavior, facial expression, the whole bit—they’re all coordinated aspects of a response that’s useful in certain kinds of situations. This doesn’t mean that every emotion has a specific function. Lots of emotions have multiple functions, and there are plenty of overlaps between the functions of different emotions. The bottom line, I argue, is that organisms during the course of evolutionary history have encountered the same kinds of situations with the same kinds of adaptive challenges, over and over again. Those that have a capacity for a somewhat standardized coordinated pattern of responses get a selective advantage.”
For irritants—such as chemicals that bother our skin—the adaptive advantage is clear. Too much of an irritant can kill us. Having a mechanism in place to help us avoid them is good for our survival. When the irritant takes on a cognitive nature, however, could the negative feeling that results also be adaptive? “As we pursue a goal, if it’s all going well, we feel great,” says Nesse. “When we experience an obstacle, we feel frustrated. And I think this may be another emotion that fits pretty nicely into this scheme.”
No one in his right mind seeks out situations that will make him feel irritated—it’s not a positive feeling—but, according to Nesse, that doesn’t mean we’d be better off without annoyance. In fact, Nesse doesn’t think any emotions are bad, really: “Everybody assumes that something like annoyance is a bad emotion or we should minimize it because having it is bad. I don’t think so, any more than anxiety is bad or sadness is bad or anger is bad—they’re all good in terms of their usefulness when they are expressed to the right degree in the right situation.”
Nesse suggests all of these negative emotions have some role in helping us survive—they encourage us to avoid things that are bad for us, for example. Maybe annoyance evolved to deter us from engaging in situations that are unpleasant, unpredictable, and out of our control. Or maybe the feeling of annoyance evolved as a by-product of some other, more evolutionarily advantageous traits. The alertness that comes from the dorsal anterior cingulate and the extra energy that comes from stress (and the abatement of oxytocin that lets us focus on selfish needs) all have a clear usefulness for humans. The fact that we accidentally turn on that series of reactions for all sorts of useless things as well may be a side effect.
Perhaps we should be thankful that nature gave us the ability to freak out, no matter what the cause.
“If you think about really simple organisms, they may not have the complex cognitive capacities that we have, but they certainly have things they find aversive, that they want to avoid,” says Paul Garrity, a developmental neurobiologist at Brandeis University. It’s all part of the drive to survive.
Garrity is interested in what’s called chemical nociception, that is, the molecules in cells that recognize irritating chemicals in the environment. These molecules sit in the surfaces of cells, poking out into the extracellular environment. When a noxious chemical floats by, they initiate a cascade of chemical changes inside the cell that protects the cell from damage. Working with fruit flies, Garrity has found evidence that a particular receptor, known as TRPA1, has a long history of helping creatures across the animal kingdom, from sea anemones to fruit flies to humans, detect irritants.
Imagine, for a moment, that you are a fruit fly, and you are hungry. You know what sounds really refreshing? A nice drop of sugar water. Yesterday, there was some near the edge of your enclosure. “Is it still there?” you wonder. You buzz over to that spot, and sure enough, it’s there. You lean in for a sip. Yuck. Ptooey. Ick. You recoil in horror. What happened?
Garrity can tell you. He put a little cinnamon in the water. Fruit flies do not like cinnamon. They will refuse to sip sugar water—something they usually seem to enjoy—if it’s laced with the spice. They will also turn their proboscises up at wasabi, raw garlic, and mustard. These plants contain chemicals that irritate fruit flies and, not coincidentally, humans as well. In small doses, they are bothersome, rather than harmful. Yet they irritate with a purpose: the feeling is usually a warning that in higher doses, these compounds won’t simply annoy you, they will hurt you.
Many chemical irritants—although not all—are irritating because they love electrons. Appropriately named electrophiles, these compounds don’t steal electrons; they insist on sharing—which is no less annoying to the compounds they are sharing with. They’re like an unwanted houseguest, says Garrity. “They’re like the guest who comes and stays and eats your food. They like your house, and they just sort of sit around.” That’s what electrophiles do.
Electrophiles don’t target only the electron-rich. They will try to share electrons with molecules that aren’t prone to making donations. “If you take something that is extremely electron-poor, then the donor doesn’t have to be as electron-rich as it might otherwise be,” says Garrity.
Electrophiles glom onto fats. They put a wrench in the gears of proteins, changing their function, Garrity says, and they latch onto DNA, which can cause mutations. DNA bases are not apt to share their electrons. (This is good news for life on Earth.) “But if you mix them with something that’s really starved for electrons, it will find those electrons and form a bond,” Garrity says. These chemical irritants that love electrons don’t play favorites. “They just go around and muck up whatever.”
Yet mucking stuff up isn’t what makes these chemicals annoying. They’re irritating thanks to a receptor that fruit flies, humans, and, in fact, all invertebrates and vertebrates share. It’s called TRPA1 (which stands for “transient receptor potential A1” and is pronounced “trip-a-one”). “In mammals, we think it’s primarily a receptor for chemical irritants,” says David Julius, a biochemist at the University of California, San Francisco, and the guy who discovered its function.
The job of receptors is to recognize specific chemicals and bind to them. Once a chemical is attached, TRPA1 acts as an alarm, sounding when electrophiles are present in or on our bodies. Without the alarm, this class of chemical irritants wouldn’t irritate us. Fruit flies that are genetically modified to lack TRPA1 happily lap up cinnamon sugar water, Garrity showed in a 2010 study in
TRPs are just one type of receptor involved in sending an irritation message. There are different receptors for histamines, which are responsible for irritation from allergies, and acids, such as when lemon juice gets squeezed in your eye. “There’s a whole host of receptors that are involved in signaling pain, irritation, and also itch. TRP channels are just one piece of the puzzle,” says pain researcher Earl Carstens, from the University of California, Davis. “It’s a big puzzle because there are lots of pieces.”
TRPs are interesting because they respond to a host of environmental assaults—hot, cold, chemicals. (A cousin of TRPA1—TRPV1—detects the capsaicin in chili peppers.) “It is a truly wide-spectrum irritant receptor,” says Carstens of TRPs. Sensitivity to a broad swath of irritants is especially true for TRPA1. David McKemy, who worked in Julius’s lab before he got his own at the University of Southern California, says the word
“The way we used to think about pain is that something bad happens and that causes a minor form of skin damage,” says Carstens. “And you have these chemicals that are released into the skin that act on pain fibers and cause pain sensation. What this means is that damage has already occurred before you have a chance to respond, and that’s how pain used to be thought of. But that’s wrong. Pain truly is a warning signal that allows you to do something before any damage occurs.”
That makes pain not only useful but essential. Randolph Nesse—who argues for the upsides of negative emotions—also wrote about pain: “Such defenses are analogous to the low oil pressure light on an automobile dashboard. In that case, it is clear the glowing light itself is not the problem; instead the light is a protective response to the problem of low oil pressure.” That was from an article titled “What Good Is Feeling Bad?” in a magazine called
The sensation we feel when a chili pepper is rubbed on our skin or tear gas gets in our eyes isn’t due to something being broken; it’s the message that something is in danger of being broken. The actual damage—say,
