The Forever Fix: Gene Therapy and the Boy Who Saved It

The Forever Fix: Gene Therapy and the Boy Who Saved It

by Ricki Lewis


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Product Details

ISBN-13: 9780312681906
Publisher: St. Martin's Press
Publication date: 03/13/2012
Pages: 336
Product dimensions: 5.74(w) x 8.42(h) x 1.16(d)

About the Author

RICKI LEWIS is a Ph.D. geneticist, journalist, professor and genetic counselor. The author of one of the most widely used college textbooks in the field (Human Genetics: Concepts and Applications, now in its 10th edition), she has also written hundreds of popular pieces on science and other topics for trade and specialized magazines, including Nature, Discover, and The Scientist.

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The Forever Fix

Gene Therapy and the Boy Who Saved It

By Ricki Lewis

St. Martin's Press

Copyright © 2012 Ricki Lewis
All rights reserved.
ISBN: 978-1-4299-4147-1



When I met nine-year-old Corey Haas, it was hard to believe that just over a year earlier, he had been well on his way to certain blindness. As a geneticist, I'd followed the incredible story of his gene therapy, and as a mom, I was curious about the young man who had made medical history.

On a dazzling Saturday morning in early December 2009, I drove forty-five minutes north to meet Nancy, Ethan, and Corey Haas, who live in the Adirondack Park. This spectacular expanse of nature is not a park in the conventional sense, but a vast swath of New York State peppered with small, older houses and log cabins nestled among towering pines, with the occasional noticeably newer vacation home of a downstater. The meandering Hudson River, only a few hundred feet across this far north, snakes through the Haas family's small town of Hadley, where Corey's parents grew up. The river is only a block away from their Cape Cod home, flooding their basement in bad snow years. I'd been in the area before, so I found it easily, but some of the reporters coming to interview the family over the past month had grown uneasy when the towering mountains blocked even the most powerful cell phone and GPS signals. But they made it — Ethan gives good directions.

Although it took only days for the researchers to realize that Corey's gene therapy had worked, they had waited a year to publish the results, to be sure the effect lasted and hadn't caused any problems. They had learned from past gene therapy fiascoes, and also knew Corey's newfound sight would be big news. And they were right, with Good Morning America setting the slightly hyped tone by describing "revolutionary surgery that could give the gift of sight to the blind." When the research paper appeared in The Lancet in November, the Haas family traveled to New York City for the very first time, where they made the rounds of the major TV news programs. Despite the intense interest, though, only a few journalists ventured north to meet Corey on his own turf.

The morning of my visit, the scent of the season's first snowfall was in the air. In the Adirondacks, you don't need a weatherman to know which way the wind blows, to quote Bob Dylan. You just have to watch the squirrels. I had to hopscotch around them as I walked up to the Haases' front door, my hands laden with my laptop, books, and a large box. The squirrels scurried everywhere, grabbing and stashing acorns in the heart-shaped crevices at the bases of the tree trunks, occasionally dashing the wrong way and bashing into the large picture window in the living room that reached almost to ground level. The squirrels knew snow was coming.

When Corey opened the door, our eyes went first to the scampering squirrels, then to each other. He gave me a huge grin, his blue eyes dancing behind thick glasses. He took my leg and guided me to a coffee table, where I dropped my armload. As Ethan and Nancy introduced themselves, Corey began rummaging around the rocks and fossils in the box, a subset of the collection I'd begun at his age. Knowing he'd only recently been legally blind, I knelt down and tried to show him how to feel the indentations of the trilobites and brachiopods. But he proudly refused all assistance, peering closely at each fossil, as I had at his age, slowly turning each one to see what different angles might reveal.

I looked around. The décor was a welcoming blue and white, the rooms unusually tidy for the home of a small boy. His toys were neatly aligned on low shelves and stacked in corners, without the clutter that continually grows in my own home. But perhaps this was a habit from the time when Corey had to memorize where every single item in a room was in order to move about. Above the couch where I sat and typed as the family talked, a shelf held a dozen of Nancy's 110-plus dolls. These were the special ones, the others inhabiting closets and a storage room, packed in with Nancy's scrapbook collection. The other walls held what can only be described as a gallery of Coreys. My favorite was a photo of Corey at about one year old, with a broad smile and thick glasses, "Corey" stitched in needlepoint below, framed in red. The earliest photo on the walls, taken when Nancy and Ethan had yet to learn that Corey had inherited an eye disease, showed baby Corey stuffed into railroad overalls, a yellow shirt, and white socks, looking off to the side as if he'd rather be anywhere else. A wall in the dining room had the words live, laugh, and love spelled out in wood, with three photos beneath each — all of the resident celebrity, Corey.

As Ethan talked and sorted copies of medical reports to give me, Corey jumped up every few minutes to show his mother a rock. I glanced at them, trying, but failing, to imagine this energizer bunny of a boy stumbling around the same living room, crashing into the furniture like the squirrels outside careening from tree to tree. But that day he rocketed around the cozy living room with ease. He showed me his handheld Nintendo and how to extract a fart noise from a container of Silly Putty–like goop, and then he asked me to name the minerals in his rocks. Periodically he'd demonstrate the hardest part of the gene therapy for him — lying ramrod still on his back. I noted subtle signs of what the family had been through. Once in a while Corey would lose his footing briefly, and Nancy's arm would instantaneously zap out to steady him, sometimes hugging him close. He didn't squirm away. Corey's independence was still new to all three of them. For years he could see only shadows, and in dim light, nothing at all.

On September 20, 2008, two days before Corey's eighth birthday, and fifteen months before I met him, the Haas family had traveled to Children's Hospital of Philadelphia — CHOP. That week, Corey underwent a battery of what had become familiar tests, plus a few new ones, and on Thursday morning was finally prepped for the procedure. Then, as Corey lay anesthetized, the eye surgeon Al Maguire snipped open a tiny flap in the left eye, the worse one, and carefully injected 48 billion doctored viruses into a tiny space just above a thin layer of colored cells that resembled patterned bathroom tile. This space and the layer of cells hug the rods and cones at the back of the eye. Corey's colored cells weren't doing their job of nourishing the precious rods and cones, which are called photoreceptors because they capture incoming light. His rods and cones had been slowly starving for years, gradually becoming too weak to send light signals to his brain to paint an image. As a result, before Corey lay down on the operating table, he saw only blurry, dark shapes. But that would change — sooner than anyone had even dared imagine.



Corey Haas was born on September 22, 2000. After an uneventful pregnancy, Nancy gave birth to the blond, blue-eyed baby, who weighed in at a respectable nine pounds.

For the first few months, all was perfect and he hit his developmental milestones ahead of schedule. "Corey was a happy baby. But the babysitter noticed that he wasn't reaching for things right in front of him, like other babies do," recalled Nancy. She worked in an office nearby, while Ethan commuted more than an hour each way to and from his job at International Paper, so they often weren't with their son during the day. Corey's parents and the babysitter wondered about Corey's peculiar habit of staring, enthralled, at lit bulbs, for far longer than anyone else would or could. When the babysitter commented that Corey never made eye contact with her when drinking his bottle, Nancy realized that she'd been aware of this too, but thought he was just too young to focus.

As the weeks went on, the new mother felt an ember of fear whenever she'd call her son's name and he'd turn, but just stare in her general direction; she didn't feel as if he was seeing her. Then Nancy noticed that he played only with toys that were lit up or that were lying in a patch of sunlight on the carpet. Something was wrong with Corey.

By six months of age, the problem became more pronounced. Not only couldn't Corey focus, but now his eyes wandered, flicking back and forth, his left eye worse than his right. This painless but unsettling condition, which the Haas family later learned is called nystagmus, is common in people who have albinism. Perhaps because Corey's hair and skin had color, the local pediatrician reassured the concerned parents that albinism didn't seem likely, and that the boy would probably outgrow the troubling symptoms.

Corey's local pediatrician apparently made no notes that indicated he suspected a genetic disease, and this is understandable; such conditions usually bring a swath of signs and symptoms, such as developmental delay, unusual facial features, defects in major organs, or constant colds from a suppressed immune system. Corey was a chubby, vibrant picture of health, adorable and active. But the pediatrician, noting at the six-month exam Corey's occasionally crossed eyes, was sufficiently concerned to refer him to the ophthalmologist Gregory Pinto in nearby Saratoga Springs, the first in a series of eye specialists who would gradually zero in on the diagnosis. Nancy and Ethan were concerned, but not alarmed. Perhaps his visual system was just developing a little slowly — not all babies focus on their parent's faces in the first weeks of life. Corey's wandering eyes seemed like something that would be simple to fix, if the condition didn't clear up on its own.

When Dr. Pinto first saw Corey, the boy was seven months old. Corey's eyes had all the right parts, but the doctor noted that the back of his eyes had unusually pale areas, "blond fundi" in the medical lingo. The most telling of the doctor's observations was Corey's fascination with lights. Dr. Pinto had seen that before, in people of limited sight trying to "self-stimulate," he told Nancy.

Except for his eyesight, Corey seemed fine, eager to go from immobile infant to active toddler. He loved to explore. At eight months, no longer content to sit and crawl, Corey was already hauling himself upright, but he was clumsy. He'd bump into things, especially when the room was dimly lit. And Corey continued to stare at lights, mesmerized.

Like a seedling seeking the sun, Corey continued to pull himself up and grab toward the lamps in the small living room. Soon he was cruising and then walking. Once he could no longer feel the surface of the shaggy carpet beneath him with his hands and lower legs, his internal feedback system was gone, and the bumping into things worsened. Yet in other ways he was right on track. He could utter a few words and even draw simple shapes. He was learning to compensate with his better-functioning senses.

At the next eye exam, Dr. Pinto picked up on a change for the worse. "Corey had started to show signs of visual difficulty. Sometimes he would crawl right into a table leg. He didn't follow objects as well as he previously had. His eyes now crossed slightly and, most significantly, he was quite nearsighted," recalls the ophthalmologist. The doctor was concerned at the rapid deterioration of Corey's vision and sent him to a pediatric ophthalmology subspecialist, Dr. John Simon, an Albany physician who had a satellite office near the Haases' home. He confirmed Dr. Pinto's findings, and prescribed Corey's first glasses when the boy was ten months old. At a follow-up visit near the end of 2001, Dr. Simon discovered some new signs: Corey's left eye turned inward, and his irises let light through in spots, as if pierced with tiny holes. But Corey was still too young for anyone to really tell what was happening, other than extreme nearsightedness. Many kids simply outgrew early visual problems. It was too early for a definitive diagnosis, but in the meantime, the glasses would help.

Corey continued to develop at a normal pace, but his vision worsened, despite doubling the correction in his glasses. At his last visit with Dr. Pinto, Corey was in the throes of the "terrible twos." He wouldn't keep still long enough for a complete retinal exam, but the doctor saw enough to realize that Corey was trying to look at objects and identify them, but he couldn't really see them. And he still stared, captivated, at the lights.

In early 2003 came the first critical connection that would catapult Corey toward gene therapy. Although he did not yet have a diagnosis, Corey saw so poorly that he was eligible for the New York State Early Intervention program, which assists young children who have disabilities or developmental delay. One day, the early-intervention provider, visiting the Haas home, mentioned in passing that she had been talking to another parent whose child had a similar visual problem.

"Where did the parent take her child?" Nancy asked.

* * *

Boston Children's Hospital is about a five-hour drive from the southern tier of the Adirondacks, counting bathroom stops and the inevitable traffic on the Mass Pike. In January, an ice storm or blizzard can derail travel plans, as can the squalls that materialize out of nowhere along the barren stretch of interstate in the Berkshires, whipping up ephemeral mini-tornadoes of blinding snow. But luck was with the Haas family on a January day in 2003. The air was clear and crisp, and they made it to Corey's first appointment at Boston Children's Hospital in record time.

They instantly liked Anne Fulton, an ophthalmologist specializing in diseases of the retina in young children. Her shock of thick white-gray hair looked a little like Corey's blond mop. Dr. Fulton listened intently to Nancy and Ethan and wrote in the medical chart, "Corey's visual behaviors are described as seeing well in good light. In low light, he crashes into the furniture, and they have wondered if this might be because he is looking at the lamp instead of where he is going. He watches the TV at an angle."

The next day, Corey was anesthetized to keep him still and given eyedrops to dilate his pupils, to do an electroretinogram, or ERG. This test shows the retinas' responses to flashes of light, and is normally a curve that dips and then sharply rises.

Corey's ERG was as flat as an Iowa cornfield.

Ophthalmologists knew that a flat ERG is a definitive sign of a certain class of retinal diseases, but since Dr. Fulton rarely had seen such a profound lack of a response, she double-checked her equipment. It was fine. The problem was with Corey's eyes. Light energy wasn't getting to his brain.

Once Corey awakened from the anesthetic, Dr. Fulton donned a device resembling a miner's helmet and gently peered at each of the boy's retinas, under light so intense it often made children (and some adults) scream. Not Corey. If he hadn't been so fascinated with all the paraphernalia, and so oblivious to the penetrating light that was much brighter than he was used to, it might have been harder to keep him still. But Dr. Fulton got a good look. In each eye, she saw that the macula, the pale area near the point that provides the sharpest vision, was too pale. It was an ominous sign.

Dr. Fulton's tentative diagnosis: albinism. Corey's stumbling in dim light suggested night blindness, but the family's pale coloring and the observation that both Nancy's and Corey's irises let in light through tiny holes suggested albinism. Perhaps Nancy actually had a very mild case of albinism, and Ethan was a carrier of the same type, and their individual mutations combined in a way that more severely affected their son's eyes. The various types of albinism are recessive, passed from unaffected carrier parents, so the fact that neither Ethan nor Nancy knew of any affected relatives didn't matter. Albinism could be passed, silently, for generations. Corey had already tested negative for the most common type of albinism, but maybe the Haas family had a rare or even unique form of the condition that affected mostly the eyes.

Eight months later, in the fall of 2003, Corey turned three and started preschool. His world now consisted of shadows even when he was in a normally lit room, and in a brightly lit room he had extreme tunnel vision. Today he acts out this early memory, tilting his head to show what he once had to do to position an object in the center of his shrinking visual field.

That October, Corey returned to Boston Children's Hospital for a more complete workup. Wen-Hann Tan, a pediatrician and geneticist, examined the squirming toddler, checking for hints of "dysmorphology" — known informally in some genetics circles as an exam for an FLK, or funny-looking kid. People with genetic syndromes often have unusual facial features that alone might simply seem quirky, but taken together may point a perceptive clinician to check particular genes and chromosomes. Corey sat still while Dr. Tan meticulously measured the dimensions of his ears, nose, and jaw; opened his mouth wide to scrutinize his palate; noted the spacing and slant of his eyes; and measured the space between his upper lip and nose. Corey's face was cherubic, bearing not a hint of anything awry.


Excerpted from The Forever Fix by Ricki Lewis. Copyright © 2012 Ricki Lewis. Excerpted by permission of St. Martin's Press.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

Table of Contents

Preface ix

Part I The Best That Can Happen

1 Meeting Corey 3

2 The Road to a Diagnosis 7

3 What's Wrong with Corey? 13

Part II The Worst That Can Happen

4 The Breakthrough Myth 27

5 Jesse and Jim 35

6 Tragedy 52

Part III Evolution of an Idea

7 The SCID Kids 71

8 Setbacks 94

9 Lorenzo and Oliver 108

Part IV Before Gene Therapy

10 Hannah 135

11 Lori 148

Part V After Gene Therapy

12 Amazing Women 177

13 The Jewish Genetic Diseases 185

14 The Patent Predicament 196

15 Chasing Moonbeams 204

Part VI Corey's Story

16 Kristina's Dogs 225

17 Lancelot 237

18 Success! 253

19 Back to Chop 268

20 The Future 290

Epilogue 305

Notes 307

Acknowledgments 319

Reading Group Guide

1. How does gene therapy differ from other types of treatments?

2. Why did it take Corey's parents, and the other parents in the book, months to realize that their children had medical problems?

3. What can a parent do when she knows that something is wrong with her child, but health care professionals do not take her seriously?

4. Imagine your young child is diagnosed with a rare inherited disease. List ways to learn about the disease, find clinical trials, and raise funds.

5. What factors would you consider in deciding whether your very young child should have an experimental treatment?

6. Informed consent guidelines from the Food and Drug Administration (FDA) state that age seven is old enough for a child to give consent to undergo an experimental procedure. Do you think that this age is an appropriate cut-off? Why or why not?

7. Paul Gelsinger, whose eighteen-year-old son Jesse died in a gene therapy experiment (Chapter 4-6), sent the author this e-mail after reading The Forever Fix:

I am glad that gene therapy is making headway. I have always felt (maybe even known) that it was a viable technology. I hope that it pans out as you hope, but please, oh please, don't make the same mistake I did and believe everything you hear or see. I am thankful that there is a great deal more honesty and oversight in the field now as a result of what happened to Jesse. . . .I guess that's his real legacy. Feel free to tell anyone that I am glad there have been some breakthroughs and that I hope many more follow.

Would you be able to be as forgiving as Paul Gelsinger? What did he mean by the mistake of believing everything? That is, which particular facts were misconstrued or miscommunicated in Jesse's sad case?

8. Lori Sames, Hannah's mom, is reaching out to all the families she can find whose children have giant axonal neuropathy (GAN). Participation of families is important in research to develop tests and treatments, but some families prefer to keep to themselves. To what extent should an activist parent like Lori try to convince hesitant families to join the group seeking a treatment?

9. How can social media help families with rare diseases?

10. What complementary therapies might ease the daily lives of children with certain inherited conditions? How can complementary therapies help or hinder the progress of FDA-sanctioned clinical trials?

11. Gene therapy for HIV/AIDS is safe and appears to be working, after nearly a dozen years in three clinical trials. Yet drugs (anti-retrovirals) have been very successful in controlling the infection. What are the pros and cons of a "forever fix" for HIV/AIDS? How does the situation for HIV/AIDS differ from that of a rare disease such as giant axonal neuropathy?

12. What criteria should researchers use to select diseases to approach with gene therapy? Knowledge of mechanism? Prevalence? Whether a famous person has it? How involved the parents are? Possibility of translation to more common conditions?

13. Why were the first gene therapies done on very rare diseases?

14. Did reading the book alter your view of the use of animals in biomedical research?

15. Why won't the gene therapies described in the book be passed to the children of the treated patients?

16. Which do you think is more dangerous to use in a gene therapy trial to deliver the genes, adenovirus or HIV? Why?

17. Under what circumstances would you have or allow your child to have gene therapy?

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