This excerpt from "The Forever Fix: Gene Therapy and the Boy Who Saved It," by Ricki Lewis, is reprinted with permission of the publisher. Also check out ReportingonHealth's interview with Lewis here.
Corey was now nearing his sixth birthday. He was making excellent progress in learning Braille, but he needed so much paraphernalia in his classroom in order to see that he and his stuff took up two seats. The teacher put him in the back of the room because his equipment distracted the other kids if he sat in the front. He remembers the isolation well. "I had a Clarity DeskMate, which is like a little computer monitor screen with an arm with a camera attached that let me see the whiteboard. I had to sit in the back." To read at his seat, Corey needed a magnifying glass and a 100-watt bulb, and still he had to keep his face rig ht next to the print.
"If Corey was in a typical classroom, where the kids would find the light bright enough to read, he could not. His pupils would dilate as far as they could, as if they were trying to pull every photon out of the room," explained Dr. Jean.
Dr. Fulton told Nancy and Ethan that Corey had inherited a different mutation, but in the same gene, from each of them. This meant they weren't distant cousins, which is always a possibility with an extremely rare genetic disease. Relatives can inherit the same mutation from a shared ancestor, such as a common great-grandparent. Ethan's genetic quirk is localized: one DNA base subs for another, like a one-letter typo. Nancy's class of mutation, called "nonsense," prematurely halts her cells' reading of the gene, releasing just a nubbin of RPE protein, if any at all. ("I always thought you were full of nonsense!" joked Ethan.) As carriers, Nancy and Ethan could see because each has a working copy of the gene. Team their two mutations in the eyes of a child, however, and his cells can't make the needed RPE65 protein at all. Corey's rods were starving -- and soon his cones would be, too.
Ethan and Nancy couldn't recall much of the Genetics 101 discussion they had with Dr. Fulton in Boston on that July day in 2006. Despite the years of doctor visits, and the mounting clues that Corey had inherited something, they were still in shock. But they managed to absorb enough to realize that each child of theirs stood a 25 percent chance of having Corey's disease. One single word stopped them from absorbing further genetic details. "I remember when I first heard the word ‘blind.' I thought immediately of all Corey wouldn't be able to do," says Nancy years later, still tearing up at the memory.
Dr. Fulton's recommendations were bleak. Corey should continue his vision support services at school and wear his glasses, she said kindly, and continue his efforts to learn Braille. He needn't return to Boston for another year, because there was nothing more they could do. She did, however, mention ongoing research, but that flew right past the distraught parents trying to comprehend that their child, their only child, was going blind from something that they had given him. The medical report for that visit ends with the prophetic words, "It is the RPE65 type of Leber congenital amaurosis that recently appears to have responded to some experimental treatment. This is a hopeful beginning." Indeed it was – but Corey's frantic parents didn't yet know it.
What they did know, finally, was the enemy: a specific mutation in a specific gene. Corey hadn't overdosed on malaria meds, or suffered a stroke, nor was he a flatulent camel. He was, however, a zebra.
Fledgling medical students learn right away the mantra, "When you hear hoofbeats, think horses, not zebras." It means suspect first the most common explanation for a patient's symptoms. Round up the usual suspects. In Corey's case the horses were night blindness and albinism, then retinitis pigmentosa. Medical geneticists, however, deal almost exclusively with zebras, most of which are caused by mutations in single genes. Even the more familiar among these, such as cystic fibrosis and sickle cell disease, are rare compared to conditions that reflect more of an environmental input, such as the common forms of heart disease or emphysema. But understanding how the rare genetic conditions happen can often explain more common ills. For example, the statin drugs that millions of people take to lower cholesterol were developed based on studying the one-in-a-million children who died of familial hypercholesterolemia, their cholesterol so high that it collected in waxy, yellow clumps behind their knees and elbows. Understanding how the mutant gene revved up the body's own cholesterol production suggested ways to induce the opposite effect.
From finally putting a name to their son's blindness until the next appointment in Boston a year later, Ethan and Nancy navigated a personal hell of helplessness and despair, as Corey's visual world continued to close in on him. They also struggled with the special guilt that comes with an inherited illness. "You think, how on earth could this happen to your son? How did I cause this? Then, how am I going to fix it?" recalls Ethan, his and Nancy's anguish easily reawakened. They'd decided not to risk having other children, and were steeling themselves for raising a blind child.
A year later, at the appointment at Boston Children's Hospital on June 28, 2007, everything changed. Dr. Fulton wrote in the record, " a new experimental treatment of gene replacement is planned. We are told that the youngest patients will be considered for this treatment is 8 years, an age that Corey is approaching." She told Nancy and Ethan to bring Corey back in a year, and then she called Dr. Jean Bennett, at CHOP.
But Corey never returned to Boston. Instead, he had gene therapy.
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Q&A with Ricki Lewis: Writing about Gene Therapy in "The Forever Fix"