She Can’t Feel Pain or Anxiety. Her Genetic Mutations Hold the Key to Eliminating Human Suffering, Scientists Claim.

5 min readHere’s what you’ll learn when you read this story:One woman’s rare genetic mutations make her unable to feel physical pain or anxiety. That can be dangerous, but her situation is now informing researchers. Scientists are studying gene mutations related to pain regulation, in hopes of developing gene therapies that could “turn down” chronic pain without eliminating pain entirely.New kinds of potential genetic pain treatments raise ethical questions, but they could relieve suffering for millions of people, a bioethicist says.When Jo Cameron had hand surgery, aged 66, she told her doctors she would not need any postoperative painkillers. Her anesthesiologist, Devjit Srivastava, was highly skeptical, yet hours later she felt absolutely nothing. Cameron checked out of the U.K. clinic having taken one regular dose of acetaminophen, which the nurses were obliged to administer, at a minimum. Intrigued, Srivastava examined her medical history and found the same pattern: Cameron had refused painkillers after a hip replacement the year prior, and on every medical questionnaire had reported her pain levels to be zero. Srivastava brought Cameron back in for testing and established—to everyone’s surprise, including the patient’s—that Cameron’s body experienced no physical pain.Cameron was diagnosed with “pain insensitivity disorder,” which covers a spectrum of conditions that spring from a well of underlying genetic differences. But her particular genetic makeup is unique among the studied cases, and less than a decade after Cameron’s clinical case study was first published, it is paving the way for the design of novel genetic “dimmer switches” for pain.Translating Cameron’s rare mutations into a gene therapy could fundamentally transform treatment for millions living in debilitating agony. “Theoretically, a gene therapy for pain is feasible,” James Cox, PhD, a University College London geneticist who unraveled Cameron’s genome, says—even if high costs mean broad public access remains years away. Reengineering human biology to mute pain is no longer a question of if, but when. The real question is who gets access to this genetic dimmer switch, and where we draw the line between ending chronic pain and stripping away a vital biological alarm system.“It may appear to be a superpower to not feel pain and certainly to not have to live in chronic pain is an advantage, but it can also be quite dangerous for the individual,” Cox said in an email. “Without it, life becomes a series of undetected physical disasters.” In childhood, individuals born with congenital insensitivity to pain frequently bite off parts of their tongues or swallow foods so hot they burn their esophagus. Without pain signals, everyday hazards can cause severe injury: A small cut or a burn is noticed late—only when patients see or smell their own blood and singed flesh.Designed to protect the body from damage, pain relies on nociception—the raw biological process where specialized sensory neurons detect physical, thermal, or chemical tissue injury and send signals through the spinal cord to the brain. But crucially, nociception and pain are not the same thing. While nociception is the physical detection of harm, pain is the complex, deeply personal perception created when the brain processes those incoming signals. “There’s not one site of the brain where you feel pain. If you do brain imaging, you see it’s a very complicated picture with lots of brain areas being activated,” David Bennett, PhD, a neurology professor at the University of Oxford, told me.Cameron appears to live a life not only free of physical pain, but one stripped of anxiety, “adrenaline rushes,” and depressive thinking.Unlike other patients who experience pain insensitivity, Cameron does not have mutations in pain receptors. Instead, she has critical alterations in pathways that regulate the amount of anandamide, a neurotransmitter, coursing through her body. Anandamide derives its name from the Sanskrit word for “bliss.” Normally, the body uses the enzyme fatty acid amide hydrolase (FAAH) to degrade endocannabinoids like anandamide, which naturally regulate pain and mood, to keep them in balance.Cameron has a mutation on both copies of her FAAH gene, as well as a rare microdeletion in a neighboring sequence that Cox baptized “FAAH-OUT.” FAAH-OUT is a long noncoding RNA—a gene-sized chunk of the genome that is transcribed into RNA—but unlike genes, does not lead to protein synthesis. Instead, studies have shown that FAAH-OUT regulates the expression of the FAAH gene.In Cameron, the function of both FAAH and FAAH-OUT is altered, building up an arsenal of anandamide in her bloodstream, regardless of what Cameron is experiencing. One 2020 article about Cameron in The New Yorker compared her physiology to being “fully baked” on marijuana. This isn’t entirely accurate because Cameron was born with the mutations, and all of her learned experiences and pain perception developed under this genetic context, Bennett says. But on the whole, it is true that Cameron appears to live a life not only free of physical pain, but one stripped of anxiety, “adrenaline rushes,” and depressive thinking.By mimicking Cameron’s genetics, together with colleagues, Cox has used CRISPR interference (CRISPRi) to target the FAAH-OUT promoter and its enhancer region, FAAH-AMP. This successfully dialed down FAAH expression by 50 percent in human cell lines. “The ideal situation is to leave acute pain sensing intact but to silence chronic pain,” Cox says. Clinical trials are being drawn up. Concurrently, preclinical gene therapies (such as those being developed by startup Navega Therapeutics, based in San Diego, California) aim to suppress the expression of a particular gene called SCN9A to silence chronic pain signals before they ever reach the spinal cord.Both Cox and Bennett (who has worked on SCN9A) insist the target of their work is chronic pain, specifically. The goal is not to switch off pain completely, which is a clinical disaster, but to turn it back down to a normal baseline. “At least one in five of the population suffer from chronic pain. It is one of the biggest causes of disability,” Bennett says. Traditional painkillers, including opioids and cannabinoids, are not wholly effective and raise the severe complication of addiction.Still, the rapid rise of genetic therapies brings to mind familiar warnings about technology spiraling out of control. What if a military state uses this to engineer painless, anxiety-free super soldiers? “I think we want to think about those things,” Jennifer Blumenthal-Barby, PhD, a bioethics professor at Baylor College of Medicine in Houston, Texas, says. Blumenthal-Barby is an expert on the biomedical ethics of pain treatments, but is not involved in the genetic studies.“But we want to not overweigh those slippery-slope concerns that are really far downstream,” she adds. These “hyped-up” scenarios can trigger political moratoria and freeze the process, leaving real people to suffer, she says. There is real hope that the unique life of Jo Cameron can safely help return a normal, pain-controlled quality of life to the millions currently suffering in silence.Dr. Elena Kazamia is a scientist and writer from Greece. Her PhD is from the University of Cambridge and she has previously worked at MIT and Harvard Medical School. She writes a Substack newsletter, called A Splash of Electric Ink, and is working on her debut book of non-fiction on algae.