Scientists were stunned to learn that Jo Cameron couldn’t feel pain, marveling at how the 74-year-old had never had a headache and miraculously made it through childbirth without so much as a whimper.
But now – after nearly a decade of forensic research into the grandmother’s superpower – they think they’ve finally cracked her secrets.
And the experts believe their discovery may even hold the key to developing better painkillers.
Mrs. Cameron, from Whitebridge, a village 25 miles south of Inverness, is one of only two people known to be carriers of a genetic mutation that allows her to live a virtually pain-free life.
It is also thought to explain why Ms. Cameron experiences faster wound healing and experiences remarkably little fear or anxiety.
Jo Cameron, from Whitebridge, near Inverness, has experienced broken limbs, operations and childbirth – without needing any medication. And she doesn’t realize she’s burned her skin until she smells scorched flesh
Jo Cameron (left) has lived a virtually pain-free life thanks to a rare genetic mutation that affects only one in millions. Mrs Cameron – pictured right with her children and husband Jim on her daughter’s graduation day – didn’t realize her case was unusual until she was 65
But academics at University College London, who discovered her DNA quirk four years ago, had no idea how it enabled the ex-teacher to defy basic biology.
test hAve has now discovered that the mutation, housed in the FAAH-OUT gene, effectively “rejects” a gene that regulates her pain, mood and memory.
Senior author Professor James Cox said: ‘The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a eureka moment and hugely exciting.
“But these current findings are where things start to get really interesting.”
‘By understanding exactly what happens at the molecular level, we can begin to understand biology.
“That opens up possibilities for discovering drugs that could one day have far-reaching positive consequences for patients.”
Ms Cameron didn’t realize she was nearly unique until age 65 when she sought help after her hip kept giving out.
She said, “I knew I was lucky, but it didn’t dawn on me that I was different.
‘I thought it was just me. I didn’t know anything strange was going on until I was 65.
“It’s called the happy gene or the forgetful gene. I’ve been annoying people by being happy and forgetful all my life – now I have an excuse.”
After being sent home three times for her lack of pain, an X-ray revealed that her hip had “nearly disintegrated.” It turned out that she had severe osteoarthritis, the main symptom of which is stiff, painful joints.
Scars on Ms Cameron’s hands after surgery healed very quickly and left her with very little scar tissue
A year later, Ms. Cameron had surgery on her right thumb to remove a small bone in her wrist at the base. She complained of “deformity and deterioration” of the finger, but no pain.
After being treated with paracetamol alone, she rated her discomfort as zero out of ten the day after she went under the knife.
In addition, Ms. Cameron once went days without realizing her arm was broken and has claimed that she only notices she is burning herself when she smells burning flesh.
Ms. Cameron’s strange condition, known medically as congenital analgesia, can be dangerous.
She said, ‘Pain is there for a reason, it alerts you – you hear alarm bells.
“It would be nice to be alerted if something is wrong – I didn’t realize my hip was gone until it was really gone. I couldn’t physically walk with my arthritis.”
Mrs. Cameron was later diagnosed with pain insensitivity by Dr. Devjit Srivastava, a counselor in anesthesia and pain medicine at Raigmore Hospital.
Years of in-depth research followed.
She made headlines in 2019 when UCL scientists announced that mutations in the previously unknown FAAH-OUT gene made her feel no pain, stress or anxiety.
It was previously believed that the region of the genome containing FAAH-OUT is ‘junk’ DNA that has no function.
The same UCL experts sought to understand how FAAH-OUT works at the molecular level, hoping to use the findings to develop new drugs.
Professor Cox and his team performed a series of experiments using CRISPR-Cas9, a gene-editing tool, to mimic the effect of the mutation on other genes.
They then checked which genes were activated in response to pain, mood and healing.
They also looked at fibroblast cells – which are needed to form connective tissue – from patients who feel chronic pain.
The findings, published today in the journal Brain, show that FAAH-OUT regulates the expression of FAAH, part of the endocannabinoid system – which regulates and controls learning, memory and emotional processing.
Mrs. Cameron’s mother (pictured in the middle with Jim) noticed that her daughter had broken her arm as a child when she saw it hanging strangely. Mrs. Cameron had had a roller skating accident three days earlier. She also doesn’t realize she’s burning herself until she smells scorched flesh
FAAH is known for its involvement in pain, mood and memory.
In Ms. Cameron’s case, FAAH-OUT “substantially rejected” FAAH.
The researchers said they have now identified the “molecular basis for painlessness,” as well as the molecular pathways that influence wound health and mood.
They also identified another 797 Mrs. Cameron’s genes that had turned up and 348 that had been rejected.
This included alterations to another genetic pathway related to wound healing.
Two other key genes that were altered were BDNF, previously associated with mood regulation, and ACKR3, which helps regulate opioid levels.
Senior study author Dr Andrei Okorokov, a pain researcher at UCL, said: ‘As scientists it is our duty to investigate and I think these findings will have important implications for research areas such as wound healing, depression and more.’
Ms Cameron’s mother and daughter claim to feel pain as normal, while her son reports some numbness.
Her deceased father Joseph is said to have ‘little need for painkillers’.