I have a weakness for stories about people whose bodies do something so unusual that researchers have to stop and reconsider how the rest of us work. Jo Cameron belongs very comfortably in that category. She lives in Scotland, experiences extraordinarily little physical pain, and spent much of her life assuming that was fairly normal. Meanwhile, most of us can identify the exact piece of furniture responsible for the last time we stubbed a toe.
What interests me about Jo is the possibility that understanding her biology could help people who live with far too much pain. Her story connects a small missing stretch of DNA with chemical signaling, gene regulation and the way we experience the world. That's already plenty to get my attention, and the details turn out to be much stranger than a single magical gene.
Her Doctors Noticed Something Unusual After Surgery
According to UCL's account of the discovery, Jo had severe degeneration in a hip joint at 65 despite experiencing remarkably little pain. A normally painful hand operation the following year brought her unusual response to further medical attention. Anesthetist Devjit Srivastava recognized that her history deserved investigation, and researchers at UCL and Oxford began looking for a genetic explanation.
The ordinary part of that story is what I find especially interesting. She had a lifetime of experience with her own body, and that was the standard she had available. We can compare notes about a headache or a burn, but we still have to translate a private sensation into words somebody else understands. Jo's experience happened to be unusual enough to reveal something researchers could investigate.
The 2019 case report records general anesthesia and a nerve block during her hand surgery, followed by paracetamol and remarkably little postoperative pain. Paracetamol is the medicine Americans call acetaminophen. The striking finding was her unusually low need for pain relief afterward, including after the block wore off. Keeping those details together makes the actual medical observation much clearer.
I think the real version is more interesting anyway. A doctor noticed a response that differed from what this operation usually produces, took the patient's account seriously, and followed the question into her biology. That sequence has a lot more substance than turning somebody into a comic-book character and calling it a day.
Two Genetic Changes Helped Explain the Picture
The researchers identified two changes together, a small deletion in a region called FAAH-OUT and a common variant in the neighboring FAAH gene that reduces the enzyme's activity. FAAH stands for fatty acid amide hydrolase. The combination helped explain Jo's unusual phenotype, the observable traits the researchers were trying to understand.
Those names are a little intimidating, which is unfortunate because the basic question is wonderfully approachable. Our cells produce chemical signals, and other parts of the system help control what happens to them. Change the way a signal is regulated and the experience connected to it can change too. With Jo, the researchers had a particularly unusual example to work backward from.
Your Body Already Makes Endocannabinoids
The relevant signaling system is the endocannabinoid system. Health Canada's scientific overview describes a collection of receptors, signaling molecules and enzymes involved in processes including pain, mood and memory. Endocannabinoids are molecules our bodies make, with anandamide being one well-studied example. The terminology connects to cannabinoid receptors, but we're talking here about an existing part of our own biology.
FAAH helps break down anandamide and other fatty-acid amides. A useful way to think about that is to consider both the arrival of a message and how it gets cleared away afterward. Both matter to the conversation. I find that second half wierdly easy to overlook because making a chemical sounds more dramatic than managing what happens to it once it's there.
Blood testing in Jo's original study found elevated anandamide and related molecules that FAAH normally breaks down, consistent with reduced FAAH function. That finding tied the genetic results to measurable chemistry. It gave the researchers another piece of the explanation, alongside the reports about how she experienced pain.
It's tempting to hear about one molecule and immediately promote it to the answer for everything, especially when pain and anxiety are involved. I keep coming back to the word system instead. Receptors, different signaling molecules and the enzymes that regulate them are all part of the picture, which makes the biology more interesting and the prospect of changing it more demanding.
The Overlooked Part of the Genome Had Something to Say
The FAAH-OUT finding also leads into one of my favorite kinds of science stories, the point at which a thing people had barely considered turns out to deserve considerably more attention. A gene that produces a protein is relatively easy to give a job description. Other stretches of DNA can take a little more explaining, and their names sometimes carry the history of how little we understood them.
The National Human Genome Research Institute explains that noncoding DNA supplies no instructions for a protein's amino-acid sequence, while parts of it have other functions, including regulating gene activity. Other regions still have functions we haven't established. So the label tells us something specific about protein coding, with a great deal left to investigate beyond that.
MedlinePlus Genetics describes how noncoding regions can provide regulatory elements or instructions for RNA molecules that influence gene activity. Long noncoding RNAs are one group of those molecules. FAAH-OUT brought that kind of regulation directly into the investigation of Jo's pain sensitivity.
I like how that changes the question. Alongside asking what a gene makes, we can ask what controls its activity and how that control fits the rest of the cell. The instruction and the regulation become equally interesting parts of the story, which is considerably more satisfying than assigning the entire job to one mysterious mutation.
The Follow-Up Research Looked at How the Regulation Works
In 2023, UCL described follow-up work examining how FAAH-OUT affects FAAH expression. Researchers used approaches including CRISPR-based experiments in cell lines and analyses of cells obtained from the patient. They investigated pathways connected with wound healing and mood alongside the regulation of FAAH itself.
The paper in Brain identified regulatory activity within FAAH-OUT and described how disrupting its transcription could reduce FAAH expression. It also investigated changes across a network of genes in patient-derived cells. This moved the explanation beyond identifying a missing DNA segment toward understanding what that segment was doing.
There's a rather large amount of work hiding inside that step. Finding an unusual genetic difference is the beginning of a question about function, and experiments help researchers test how the pieces connect. I find that process pretty exciting, even when the resulting explanation requires stopping to look up another abbreviation. Biology seems determined to make us earn every interesting detail.
Fast Healing Is an Interesting Clue
Jo reported that cuts and burns often healed quickly with little residual scarring. Her clinical examination also documented scars on her arms and hands, a detail that keeps the story grounded. The follow-up research examined gene pathways associated with healing, giving researchers possible mechanisms to investigate rather than a demonstration of scar-free skin regeneration.
I understand the appeal of jumping straight from that to better wound care. Healing is an ordinary word for a remarkably complicated result, and finding ways to improve it could matter enormously. The interesting question is which parts of this biology could eventually help with a specific problem, under conditions where we understand the benefits and risks.
Claims about reversing aging or erasing every scar would add an entirely different set of promises. I'd rather stay with the question the research actually opened, how gene regulation might influence repair. A useful clue can be worth a great deal while researchers are still figuring out what to do with it.
Pain and Anxiety Have Connections Worth Understanding
UCL's original account also describes very little anxiety and fear, an optimistic disposition and everyday memory lapses. Those observations made the broader pattern interesting to the researchers, particularly given the signaling system involved. They give us information about Jo's reported experience alongside her unusual pain sensitivity.
I can see why this part captures people's attention. The prospect of feeling less frightened or overwhelmed has an immediate emotional appeal, while the biology asks much more specific questions about which processes are changing and why. Those questions deserve room, especially when the eventual hope is helping people whose experiences differ from Jo's.
A report about an unusually low level of anxiety also leaves plenty of a person's life undescribed. It tells us about the traits under investigation, rather than giving us access to every emotion or memory they've ever had. I want to keep that distinction in the story because Jo is a person participating in research, with a life considerably larger than the molecular pathway that made her famous.
Pain Is More Complicated Than a Damage Meter
The International Association for the Study of Pain distinguishes pain, a personal sensory and emotional experience, from nociception, the nervous system's processing of potentially harmful stimulation. Biological, psychological and social factors can influence pain. Someone's report of pain deserves respect, and the experience can affect daily functioning and well-being as well as providing protection.
That helps explain why I find Jo's story so thought-provoking. Physical injury and how much it hurts are connected through a complicated system. A person can need medical attention while experiencing very little pain, just as somebody else's pain can be deeply disruptive. The first situation gives researchers one kind of question, while the second gives us a reason to care about finding better answers.
Her history included cuts and burns that she could overlook until other clues drew her attention to them. I think about how often a small sting or sudden discomfort makes us stop what we're doing. For all the times I'd happily turn that interruption down, it also carries information about the world we're moving through.
Could This Become a Useful Treatment?
This is where the possibilities get exciting and the experiments become especially important. A lifelong genetic combination is a different starting point from giving a medicine to somebody with an established pain condition. Researchers need to determine which part of the pathway to target, how strongly to change it, and what happens elsewhere when they do.
There's already an instructive example in the FAAH research. In a 2012 randomized trial involving 74 people with knee osteoarthritis, the FAAH inhibitor PF-04457845 substantially reduced the enzyme's activity and increased its chemical substrates, but pain relief was similar to placebo. That result belongs to that drug and that condition, while showing why changing the chemistry and improving someone's symptoms have to be tested separately.
The FDA's explanation of gene therapy makes the next requirement clear, clinical testing for safety and effectiveness before a product can be marketed. The FAAH-OUT experiments discussed here examined mechanisms; they weren't a clinical trial of a Jo-inspired treatment in patients. That is still a meaningful stage of research, and it gives future work a more specific direction.
I've also written about CRISPR and genetic editing, and stories like this remind me how much the goal matters. Helping somebody manage persistent pain while retaining useful protective sensation would be a very different ambition from making everybody permanently painless. It calls for careful choices about what improvement should look like to the person receiving it.
The Part of Jo's Story That Stays With Me
What I keep coming back to is that this began with somebody being listened to. An unusual response after surgery became a medical question, and that question led into a region of the genome with a role researchers could investigate. The possibility of helping other people grew out of paying attention to one person's experience.
I find that encouraging in a very practical way. We have an enormous amount left to understand about bodies, including experiences that sound ordinary until we realize how differently another person has been living them. Jo's story gives us a particularly striking example, with enough real biology behind it to keep my curiosity occupied for quite a while.
I'd be thrilled if this line of research eventually contributed to better pain relief or wound care. For now, the discovery itself is already something worth sharing, a reminder that useful questions can begin with a response everybody nearly accepted as normal. I'm glad her doctors kept asking.
Sources
UCL, 2019. The discovery of Jo Cameron’s unusual pain sensitivity.
Habib and colleagues, 2019. The original FAAH-OUT case report.
Health Canada. The endocannabinoid system and its components.
Brain, 2023. Molecular basis of FAAH-OUT-associated pain insensitivity.
International Association for the Study of Pain. Pain terminology and explanatory notes.
Huggins and colleagues, 2012. A randomized trial of FAAH inhibition for knee osteoarthritis pain.
U.S. Food and Drug Administration. Gene therapy and clinical testing.
