“A World Without Pain: Does Hurting Make Us Human?”, 2020-01-06 (; backlinks; similar):
Cameron is entirely insensitive to physical pain. As a child, she fell and hurt her arm while roller-skating, but had no idea she’d broken it until her mother noticed that it was hanging strangely. Giving birth was no worse…Cameron was having a trapeziectomy, an operation to remove a small bone at the base of the thumb joint. Though her hands never hurt, they’d become so deformed by arthritis that she couldn’t hold a pen properly. She’d had a similar experience with her hip, which had recently been replaced; it didn’t hurt, but her family noticed that she wasn’t walking normally. She saw her local doctor about it several times, but the first question was always “How much pain are you in?” And the answer was always “None.” (“The third time I was there I think they figured, ‘We’ll just take an X-ray to shut this woman up’”, Cameron told me. “Then the X-ray came in and it was really bad. Everything was all distorted and mangled and crumbling. He said, ‘Wow. This has got to be done.’”)…Cameron is beguiled by the idea that she can help alleviate others’ suffering—she remembers the terrible migraines that tormented her mother. Her father, however, was pain-free. “I never saw him take an aspirin”, Cameron said. “I’m convinced he was the same as me, because I never heard my father complaining about any pain, ever. He died suddenly, of a brain hemorrhage—I think other people would have had a warning.”
People with severe congenital neuropathy tend to die young, because they injure themselves so frequently and severely. (Without pain, children are in constant danger. They swallow something burning hot, the esophagus ruptures, bacteria spill into the internal organs, and terminal sepsis sets in. They break their necks roughhousing. To protect some patients, doctors have removed all their teeth to prevent them from chewing off their tongues and bleeding to death.)
Cameron does not have neuropathy: she can feel all the sensations the rest of us do, except pain. The most striking difference between her and everyone else is the way she processes endocannabinoids—chemicals that exist naturally in every human brain. Endocannabinoids mitigate our stress response, and they bind to the same receptors as the THC in the kind of cannabis you smoke. Normally, they are broken down by an enzyme called fatty acid amide hydrolase, or FAAH. But Cameron has a mutation on her FAAH gene that makes the enzyme less effective—so her endocannabinoids build up. She has extraordinarily high levels of one in particular: anandamide, whose name is derived from the Sanskrit word for “bliss.” About a third of the population has a mutation in the FAAH gene, which provides increased levels of anandamide. “That phenotype—low levels of anxiety, forgetfulness, a happy-go-lucky demeanor—isn’t representative of how everyone responds to cannabis, but you see a lot of the prototypical changes in them that occur when people consume cannabis”, said Matthew Hill, a biologist at the University of Calgary’s Hotchkiss Brain Institute, who was a co-author of the Cameron paper. The FAAH gene, like every gene, comes in a pair. People who have the mutation in one allele of the gene seem a little high; people who have it in both even more so. Jo Cameron is fully baked. “When I met Jo for the first time, I was just struck by her”, Cox, an affable forty-year-old with a scruffy beard, told me, one afternoon in his lab at U.C.L. “She was very chatty. Did you notice that?” “I said to her, ‘Are you worried about what’s going to happen today?’ Because she was meeting our clinicians to have a skin biopsy and do quantitative sensory testing—pain-threshold tests. She said, ‘No. In fact, I’m never worried about anything.’” Cox told me that it was difficult to get through everything in the time they’d allotted, because Cameron was so friendly and loquacious with the scientists, even as they burned her, stuck her with pins, and pinched her with tweezers until she bled. This imperviousness to pain is what makes her distinct from everyone else with a FAAH mutation. They, like even the most committed stoners, can still get hurt.
I asked Matthew Hill—a renowned expert on cannabinoids and stress—if there was any downside to Cameron’s biology, and he laughed out loud. “Yes! From an evolutionary perspective, it would be tremendously destructive for a species to have that”, he said. Without fear, you drown in waves that you shouldn’t be swimming in; you take late-night strolls in cities that you don’t know; you go to work at a construction site and neglect to put on a hard hat. “Her phenotype is only beneficial in an environment where there is no danger”, Hill asserted. “If you can’t be concerned about a situation where you’d be at risk of something adverse happening to you, you are more likely to put yourself in one. Anxiety is a highly adaptive process: that’s why every mammalian species exhibits some form of it.” Unlike other pain-insensitive people, Cameron has made it into her seventies without getting badly hurt. Sometimes she realizes that she’s burning her hand on the stove because she smells singeing; sometimes she cuts herself in the garden and sees that she’s bleeding. But none of that has been severe, and Cameron did raise two children safely into adulthood. “The human brain is very capable of learning, ‘This is what’s appropriate to do in this situation’”, Hill said. Cameron’s relative cautiousness may have developed imitatively. “And there may not have been that much threat presented to her—she’s lived in a rural community in Scotland”, he concluded. “Maybe she hasn’t had to deal with that much that would physically or emotionally harm her.”
One complicating question is how much of Cameron’s Cameronness is really a consequence of her FAAH mutation and FAAH OUT deletion. She has plenty of other genes, after all, and her upbringing and her early environment also played a role in making her who she is. Since the paper was published, Matthew Hill has heard from half a dozen people with pain insensitivity, and he told me that many of them seemed nuts. “If you had this phenotype and weren’t a generally pleasant person like Jo—maybe you’re, like, a douche-y frat boy—the way that you would process this might be entirely different. Our whole perception of this phenotype is explicitly based on the fact that it was Jo who presented it.”