Genetic testing opens doors -- but doesn't always lead to solutions
Genetic tests allow doctors to diagnose disease and patients to glimpse their medical future, but the knowledge of what's in your DNA doesn't always help. One English man discovered that the tests didn't change his life -- and in fact left him with a tough question.
In a corner of his home in Carlisle, England, Grahame Lancaster keeps a box of framed photographs.
He pulls one out. It shows fifty police officers arranged into rows.
“That’s me in the back row,” he said. “The big lump. Bigger than everyone else there, I think.”
He was only 22, but he was formidable — 6-foot-4, 250 pounds, and confident. He served with the Greater Manchester Police.
“My favorite times were nights,” he said. “Catching criminals. I always used to pride myself on being able to catch most people.”
Aside from the paperwork, he loved the job. But a few years after that photograph was taken, he started getting odd remarks from his fellow officers. They said he smelled like rotting fish.
Following His Nose
“I just thought it was maybe something I’d eaten, even though I was never a great fish-eating fan,” he said. “So I couldn’t really understand where it was coming from.”
One officer suggested the odor came from Lancaster’s hair gel, but that didn’t explain it.
The comments grew more frequent. Suspects told Lancaster that the interrogation room reeked of fish. Defense attorneys made comments too. So Lancaster went to see his doctor.
“He basically said it was all in my head,” Lancaster recalled. The doctor suggested he bathe with strong soap.
Lancaster began showering up to four times a day. He caked on the deodorant. But within fifteen minutes of showering, the comments would start again.
The remarks became harder and harder to stomach.
“Because people make the comments, you then think that people who aren’t making comments can still smell it, but they’re not saying anything,” he said. “So you then start to become paranoid.”
A Genetic Discovery
Around that same time — in the late 1990s – British scientists discovered a gene that causes a rare condition called trimethylaminurea, or TMAU.
“TMAU is a disorder in which people are unable to complete the metabolism of a small molecule called trimethylamine,” said scientist Elizabeth Shephard of University College London. “That small molecule is derived from the ordinary foodstuffs that we eat such as eggs, soya, meat.”
In most people, an enzyme breaks down trimethylamine in the liver, but people with TMAU excrete the molecule in their urine, breath, and sweat.
And that molecule, trimethylamine, is what gives rotting fish its distinctive odor. In fact, TMAU is sometimes called fish odor syndrome.
TMAU can be triggered by liver or kidney disease, but it can also be hereditary — caused by the gene Shephard co-discovered — although the symptoms may not appear until adulthood. The genetic form of the condition is rare, affecting perhaps one in 40,000 people.
In the case of Grahame Lancaster, a medical researcher recommended he take a urine test to see if he had TMAU. It came back positive.
Lancaster was relieved. “It’s a definitive medical diagnosis that you’ve got something wrong with you,” he said. “It’s not your fault. It’s not the fact that you’re unhygienic.”
Hope and Disappointment
Once Lancaster knew what was wrong with him, he set about trying to fix it. Doctors recommended he keep a diary to track what foods made the odor better or worse.
It didn’t help.
Changes in what he ate didn’t reduce the smell. He grew even more embarrassed and self-conscious.
“[It] ruined the enjoyment of the job,” he said. “It kind of destroyed it all for me.”
The test that had given him the diagnosis had given him hope that things would change. When they didn’t change, he spiraled into a severe depression.
Lisa Claire Uren, Lancaster’s girlfriend at the time, said he was hard to get along with.
"He just wasn’t himself,” she said. “And I just didn’t know what to do — couldn’t do anything, couldn’t say the right thing. I couldn’t see us ever coming through it, really.”
Things fell apart for Lancaster at work, too. He lost focus. He went on medical leave for a year and then was discharged from the force.
His career as a police officer was over — not because he smelled like fish, but because of the resulting depression.
Lancaster said part of what made things so difficult emotionally was that he assumed the discovery of the TMAU gene meant that a cure was right around the corner.
Yet with many inherited conditions, including TMAU, the discovery of the faulty gene has not led to a treatment or cure. The science has proven more complicated than many expected at the beginning of the genomics revolution.
And there are additional obstacles for rare and non-life-threatening conditions like TMAU.
Ian Phillips of Queen Mary, University of London, a co-discoverer of the TMAU gene, said he can’t convince funding agencies to invest in the research needed to develop a cure.
“It’s frustrating because, having identified the genetic basis of the disease, we are no longer able to follow that up in any meaningful way that would be of use for the patients,” he said.
New Test, New Questions
Even without a cure, things have improved for Lancaster.
He gradually came to terms with his condition. He took up a more suitable career in information technology. His new job has less stress and no physical demands, so he is less likely to sweat and produce the fish odor.
His relationship with Uren improved, and they got married.
By this time, there was another test for TMAU — a genetic test that could identify the specific mutations that caused the disorder. The test could tell family members if they’re likely to develop the condition, even if they don’t currently show symptoms.
Lancaster has a daughter, Emma, and he was faced with deciding whether she should be tested.
“My main concern was whether I’d passed on the defect to Emma,” he said. “If she’s going to get it, I’d rather be pre-warned and pre-armed.”
Grahame and Lisa Lancaster decided to test Emma when she was a year old. It came back positive. Sort of.
Emma had inherited a faulty copy of the gene from her father, and a somewhat faulty version from her mother. That means Emma may develop a mild form of TMAU later in life.
The test result caused the parents to confront a new question. Should they tell Emma, even though she may never exhibit the symptoms? What good would the information do her?
It’s similar to the dilemma many people face who’ve been tested for genes linked to diseases, like Alzheimer’s, for which there’s no good treatment or cure. If you find out you’re at high risk, what do you do?
Lancaster realizes there’s a big difference between dementia and the condition afflicting him, but he said TMAU is nothing to laugh at.
“One of the most evocative things is your (sense of) smell,” he said. “Sometimes you smell things [and] it brings back pleasant memories. I read in some article that the smell of rotten fish is one of the worst things you could ever smell. So it’s just unfortunate that TMAU doesn’t smell of roses.”
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