Medical mysteries and the incredible quest to solve them
For more than a decade, a crack team of experts led by Dr Euan Angus Ashley, Professor of Medicine and Genetics at Stanford University and the Head of Stanford Center for Undiagnosed Diseases, has been bringing new hope into the lives of patients and their families with genetic-based diseases.
This has all been thanks to the rapid advancement of genomic-based medicine which, when combined with detective work worthy of Sherlock Holmes, can now pinpoint the cause of diseases that have previously been complete medical mysteries.
In this exclusive article, Dr Ashley, author of fascinating new book The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them, shares one such inspirational patient story, about two brave little boys—Carson and Chase—who were losing their mobility to an unknown illness.
By Dr Euan Angus Ashley
PHOTO CREDIT: ANDREW ROSS-PERRY
If he just kept searching, he might find it. The right search term, the elusive website, the next link—out there on the internet, somewhere, was the answer. It was late—the wee hours—and Danny Miller, a youthful 40-something with a bright smile and close-cropped sandy brown hair, was up, as usual, peering at his computer screen. A communications consultant with a degree in history and a lifelong thirst for knowledge, he had finished work, commuted from his office in the city 15 minutes north to his home in the San Francisco Bay Area, checked in with his wife—herself exhausted from ferrying their kids to appointments all day long—ate dinner, then sat down at his computer, wiped away his own fatigue, and started searching. He needed answers. Fast.
Danny and Nikki Miller had given birth to a bouncing baby boy named Carson a few months earlier. He was blonde haired, blue-eyed, bubbled with energy, and was the light of their lives. He developed normally at first but, as he approached one year of age, instead of moving on from cruising the furniture to walking independently, instead of picking up a fork or spoon and feeding himself, instead of forming those “mamas” and “dadas” into strings of recognizable words, he started to slip. His mental acuity was moving forward, but his motor skills were stuck in reverse. Their GP referred them to a behavioural specialist then on to a developmental specialist, then there was a neurologist, and then another. None had any answers.
Carson’s younger brother, Chase, was born a year later and blessed with the same infectious smile, the same energy, the same blonde hair and blue eyes of his older brother. It was an energy that his mum and dad could only aspire to. “My role is the researcher and the medical man, I guess,” Danny told me a few years later. “But my wife is the master scheduler and she handled juggling the schedule, taking them to and from the different therapies and appointments.”
Over the next year, as they watched Chase follow the same developmental path as his older brother, as they contemplated two sons who couldn’t feed themselves, form words, or support their growing bodies, the reason became clear: this was a genetic disease.
Dr Euan Angus Ashley, who was born in Britain, is a pioneer in the field of genetic medicine. He says that advances in genetic sequencing means that many more families can now bring their agonising medical odysseys to an end.
Carson had been given the diagnosis “cerebral palsy” by one neurologist, but this was an unhelpful label (meaning literally ‘brain paralysis’) that didn’t explain what happened or how. It certainly didn’t help with the guilt. “We blamed ourselves, you know,” Danny said. “Did I drink too much in college? Or, you know, have I not taken care of my body?”. To outsiders, the answers were obviously “no” but, when you are desperate, you first look inside.
They had seen five neurologists (brain scans had shown abnormalities in the motor area near the base of the brain) and geneticists, too. But even those specialist genetic tests provided no answers. Danny went back to the internet.
Around this time, one specialist suggested a referral to the Undiagnosed Diseases Network. This is a group of doctors of which I am a part who take on the hardest cases in medicine. When there is nowhere else to turn, patients turn to us to end their medical “odyssey” (a term derived from the Greek Epic tragedy of that name, itself named for the long and arduous journey of its protagonist). We use various approaches to solve medical mysteries. Some cases are solved by the ‘Sherlock Holmes’ method (most people don’t know that author Arthur Conan Doyle, himself an eye doctor, based the character of Sherlock Holmes on a Scottish surgeon with an eye for detail). In the real world, just one out of 10 of the cases are solved this way using existing knowledge and deductive reasoning. A whopping eight out of 10 cases are solved by a newer approach: sequencing our patients’ genomes.
The first human genome ever to have its letters spelled out (sequenced) cost $3billion dollars and took 10 countries 10 years to complete. Now it is possible to sequence a genome for a few hundred dollars (this change is the equivalent of buying a Ferrari today for one penny!). But just as important as our ability to sequence the genome is our ability to understand it. We use big computers and crunch through billions of data points to try to find answers for our patients. And it really works. When patients come to California to our site of the Undiagnosed Diseases Network at Stanford University, we are able to solve the mystery more than 40% of the time. Usually, the diagnosis points directly to a change in medical management or a potential treatment. It saves money too—bringing the genome earlier in the diagnostic “odyssey” could save 94% of medical costs.
In new popular science book The Genome Odyssey, Dr Euan Angus Ashley reveals how genomic medicine is transforming 21st century healthcare, sharing many uplifting stories of patients and their families who have benefitted from this medical revolution.
When Danny and Nikki brought Carson and Chase to us, we sequenced the entire family. When the data came back, we were dumbstruck. Despite the hundreds of tests they had undergone, despite seeing dozens of doctors over several years, despite hundreds of sleepless nights, the answer was right there in front of us. The boys had each inherited one genetic variant from each parent that disrupted both of their copies of an important gene called ‘MECR’. This gene’s protein plays a pivotal role in the mitochondria, the “power plants” of our cells. And the most susceptible cells are those at the base of brain responsible for movement, the exact area, in fact, found to be abnormal on the boys’ brain scans. On that day, Carson and Chase became the eighth and ninth patients in the world to be diagnosed with MEPAN syndrome.
The diagnosis brought answers and an end to their medical odyssey. Now they all knew the size and shape of the enemy. They had a name, a real diagnosis this time, not a nondescript label. Their guilt was lifted; they realized that their boys’ condition was not a result of something they had done, something they could have prevented. It also brought an end to the endless testing and listening to doctors scratching their heads and saying, “I’m sorry. We just don’t know.”.
The diagnosis also brought something else: a search term. Now Danny could narrow down those millions of web pages. He started researching the MECR gene and MEPAN syndrome. He read scientific articles. He studied biochemical pathways. He found out that loss of the MECR gene leads to a lack of a several important substances, one of which was called ‘lipoic acid’. Lipoic acid is critical to many of the “power pathways” inside cells. Without it those cells in the brain run out of energy. If only, he thought, there was a way to replace this important substance. His first thought was that if it even existed at all, it was likely to be hugely expensive, like a gene therapy. So, imagine his surprise when he found out that lipoic acid was a supplement that could be bought on Amazon … for $16 a bottle.
Thanks to the help of Dr Ashley and his team at Stanford University, Carson (left) and Chase (right) can look forward to a brighter future. Photo Credit: Andrew Ross-Perry.
After years of late nights, after the emotional stress of adapting their lives to the special needs of their special boys, after harrowing doctor’s visit after doctor’s visit, part of the answer to the boys’ condition was just a few clicks away, on the internet.
When I spoke to Danny a few months later he mentioned that the boys’ deterioration had seemed to stabilize on the new supplement. He mentioned their neurologist even believed there was some improvement. “That’s a huge thing for us,” he told me. Danny has now started a foundation for MEPAN syndrome, focusing his late-night computer sessions on helping other families affected, raising money to fund research into a cure, and telling anyone who will listen about the transformative potential of understanding our genome.
The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them (St. Martin's Press) by Dr Euan Angus Ashley is out now on Amazon in hardcover, eBook, and audiobook formats, priced £22.99, £9.49, and £20.47 respectively. For more information visit www.genomebook.info.
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