Savior Parents

By Elizabeth Weill

Jannine and John Cody were packing to move from Sheppard Air Force Base in Wichita Falls, Texas, to Brooks Air Force Base in San Antonio in 1985 when a military doctor gave them some devastating news. Their 6-week-old daughter Elizabeth was missing part of her 18th chromosome. To explain what that meant, the doctor showed Jannine a textbook with a horrifying picture and caption that she still keeps in her files. It read, "They are probably the most seriously afflicted among carriers of chromosome abnormalities. They maintain the froglike position observed in infants and are reduced to an entirely bedridden and vegetative life." The young mother was incredulous. "That just didn't jibe with what I was seeing," Cody vividly recalls. "It had been raining for a week, everything was wet, the packers were angry. I had a 3-year-old, a 6-week-old and a mother-in-law to deal with. I was on total overload, so I said to myself, O.K., this doesn't quite fit; she doesn't seem like a vegetable. I'll deal with that later."

Elizabeth's first year included three surgeries to fix a cleft palate and a cleft lip. By age 2, she had slipped far behind on the growth charts. Her pediatrician seemed to think that was inevitable, but her mother demanded that Elizabeth's symptoms be treated, a radical notion at the time. She took her daughter to an endocrinologist, who put Elizabeth on daily injections of human growth hormone, a therapy that caused her to grow like a weed and blossom developmentally as well. When Elizabeth had difficulty learning to speak, Cody pushed for her to see a neurologist, who determined that the problem had more to do with the impairment of her hearing than with her intelligence. The 3-year-old was fitted with a hearing aid and began learning sign language.

The journey to save Elizabeth took both mother and daughter to unexpected places. Cody went back to college and earned a Ph.D. in human genetics at age 42. Her dissertation topic: syndromes of the 18th chromosome. Today this former homemaker and president of her local embroiderers' guild conducts genetic research at the University of Texas Health Science Center. Her work has helped raise Elizabeth's IQ into the normal range and has provided a model for helping the approximately 500 other kids in the U.S. with the same defect. Cody also set up the Chromosome 18 Registry and Research Society--a foundation that connects affected families with one another and funds research.

This month Cody will reap a huge personal reward for her efforts: Elizabeth will graduate from high school. A few years ago, Cody sat watching Elizabeth's pep squad perform at a football game, wearing red, white and blue, the school colors. "Suddenly I'm watching, and I realize I can't pick her out of the crowd. She wasn't so bad!" says Cody. "I just burst into tears. I never ever thought I would see the day when she'd just be one of the girls in high school, out there on the field with all the other kids. It was amazing."

Being a parent brings out the most extreme traits in all of us--capacities for love, fear, persistence you never knew you had--and those traits are only magnified when a kid is in danger. You stay up all night when your daughter spikes a 101DEG fever. You drive across town in five minutes flat when your son falls out of a tree. But parenting a child who has a serious genetic disease transcends that entirely, as movies like Lorenzo's Oil have shown. It turns Clark Kents into Supermen and former science-phobes into experts in molecular biology. "For a long time in the pediatric community, [the attitude was] if you have a major chromosomal abnormality, you're going to not grow well, you're going to be developmentally delayed, you're going to be mentally retarded, and there's not a darn thing we can do about it," says Dr. Daniel Hale, a pediatric endocrinologist who works closely with Cody. These days the situation is different. At the molecular level, genetic diseases are better understood, and new avenues are opening for dealing with them, thanks in part to the advocacy of parents like Cody who embrace the notion that kids with chromosomal abnormalities have a right to reach their fullest potential.

Particular Clark Kents, of course, turn into particular superheroes because of varying talents and inclinations. Leslie Gordon and Scott Berns, for example, were both multidegree doctors--she has an M.D. and a Ph.D., he has an M.D. and a master's in public health--when a doctor friend diagnosed progeria in their 21-month-old son Sam, now 7 (the rare disease causes accelerated aging and often leads to death by early adolescence). The next day, Gordon took a leave from her training in pediatric ophthalmology. Within nine months, she created the Progeria Research Foundation to bring attention to and research funds for the disease, which affects just 1 in 4 million babies. "There was nothing out there. Zero," says Gordon from her home in Foxboro, Mass., her voice brimming with fierce enthusiasm. "I was surprised because as a doctor, you train, you train, you train, and when you get out there you realize there are holes."

Gordon and Berns are committed to the idea that Sam, who inhabits the body of a 70-year-old, should just be a kid. Currently he's obsessed with baseball, school and drums, and when a new friend informs him he has no hair, he says, "Tell me something I don't know. Let's go play." Gordon, in just over five years, has started a tissue bank, raised serious money and lured top scientists into studying her son's disease. In October 2002, she, along with an international team, succeeded in isolating the progeria gene. Progeria, it turns out, is caused by a tiny point mutation in a child's DNA, a one-letter typo in the chromosomal book. But even after that research triumph--the culmination of an 11-month, white-hot burn of constant phone and e-mail conversations--Gordon did not take a break. Sam, she reasons, has no time to waste. A stroke could hit at any time, and the same is true for the more than 50 other kids with progeria whom Gordon has come to know and love. "Somebody called me a barracuda once, and I said thank you," Gordon says. "You can't hand a child a paper saying we found the gene, and here, you're cured. Isolating the gene was the end of Chapter One. We now have a gene that leads to a protein defect that researchers can sink their teeth into. Fantastic labs can ask fantastic questions. We can pull in a lot more terrific researchers, ask better questions and start moving toward treatment."

Taking on the responsibility of finding a cure for your child's rare genetic disease can be both comforting and painful, like all parental obligations, except in this case the stakes aren't seeing a child's soccer game vs. working out, but seeing your child's future birthdays vs. (perhaps) not blaming yourself if you don't.

"You don't want to ever have to tell your kids someday that you didn't try your best," says Brad Margus, a Harvard M.B.A. and the former owner of a Florida shrimp-processing company who switched careers after discovering that two of his four boys had a rare, degenerative disease. "Being a dad, you're expected by your kids to be able to fix anything, right? So they're counting on you to do something about it," says Margus, who is now CEO of Perlegen Sciences, a Silicon Valley biotech firm.

Margus' nightmare started when he and his wife Vicki still had three boys in diapers, and his second eldest, Jarrett, then 18 months, developed difficulty walking and his speech slurred. At first doctors thought the cause was mild cerebral palsy. Then around his 18-month mark, Margus' next eldest boy, Quinn, started developing the same symptoms as Jarrett's, which suggested that the problem was genetic. The boys endured blood tests, spinal taps, muscle biopsies. After spending $60,000 and turning up nothing, the Marguses took their sons to see Dr. Jean Aicardi, a world-famous French neurologist who happened to be visiting Miami Children's Hospital. "In the first five minutes, he saw our kids and said, 'It looks an awful lot like ataxia-telangiectasia,' which we couldn't even pronounce. 'I assume you've tested for this?' All it takes is a $20 blood test. The local doctors just looked at their feet." The Marguses recognized the name (it's pronounced ay-tack-see-uh teh-lan-jick-tay-sha), but all they knew was that A-T was really bad. At home that night they read that about 40% of kids with A-T get cancer by age 12; 100% deteriorate neurologically, so they're in wheelchairs as early as age 8; most die of lung problems or cancer by their late teens or early 20s. "You kind of go through a grief process," Margus says. "Your kids aren't dead, but the kids you thought you had are gone."

Like progeria, A-T is what might be called a superorphaned disease. It affects so few kids--just 400 in the U.S.--that scientists and drug companies don't bother with it. So Margus began applying his business brain to the problem of how to find a cure. He broke it down into smaller problems, assembling a list of things he needed to learn about: molecular biology, how the government funds research, how you capture the interest of top-notch scientists, what lobbying is all about. He decided his approach would be to pollinate as many excellent labs as possible, funding postdocs to work under superstars and hoping that whenever researchers discovered something relevant, they might at least ask themselves, Could this help Brad's kids? "Early on, you're naive enough that you don't know how challenging the problem really is, so you give it a shot." The result? Margus has raised more than $15 million to date, and he funded the research that isolated the A-T-mutated gene nine years ago.

Still, Margus sounds distinctly sad. Sure, he has raised a lot of money and even made a savvy career switch that puts him in regular contact with executives from five of the top 10 pharmaceutical companies. Yet, in his mind, "so far we haven't done squat." His kids, now 13 and 15, are deteriorating daily. This summer he hopes to move his family from Florida to California, where he spends most of his time, but first he will need to retrofit a house "for two teenagers in power wheelchairs who can't control their motor skills very well, so they take out huge chunks of drywall." When his boys ask their father about his work, Margus is honest. "Quinn is quite tough on me," Margus says. "He asks what those researchers are doing. And candidly, I have to say that we've failed. We've set up a center at Johns Hopkins, so at least there's one place in the world that's accumulating a lot of data on the kids. But as far as a treatment or cure or even slowing the progression of the disease, we still haven't done it."

The struggles of parents like Brad Margus and Leslie Gordon are less lonely than they were in the pre-Internet era. Numerous websites help such parents reach out and learn from one another; among them are sites created by the Genetic and Rare Diseases Information Center at the National Institutes of Health and the Genetic Alliance, an advocacy group. This June in San Antonio, Jannine Cody is convening the first World Congress on Chromosome Abnormalities. More than 1,000 parents, doctors and researchers are expected to attend. Sessions will range from "Neurological and Anatomical Imaging" to "Potty/Sleep Solutions." The event is the culmination of 15 years of work, with twin goals of building stronger advocacy groups for children with chromosomal abnormalities and establishing a nucleus of scientists dedicated to addressing their problems. "Somebody ought to give that lady a MacArthur," says Dr. Hale.

On a recent afternoon, Elizabeth Cody comes bounding down the stairs to greet her mother, who has just returned from work. There is nothing froglike or vegetative about the bright-eyed 19-year-old, who flops onto the sofa and expresses relief that her mother has remembered to bring home a chart showing exactly which part of her 18th chromosome is missing. "A boy at my school used to make fun of me, so I wanted to show him this," Elizabeth explains. After graduation in May, Elizabeth plans to attend a local community college, and then become a teacher's assistant in a hearing-impaired classroom and perhaps move out to California. One thing she can count on: her mother will be cheering all the way.