The hope
This is Chapter 2 of the eight-part series Lincoln’s Shot. Click here for the other chapters.
On nights when Maggie Hoyle-Germann took the long, lonely late shift, watching over her son, she scrolled through Facebook.
Sorority sisters with cocktails were posting selfies. Co-workers were sharing photos of their kids at the beach. All her friends were leading lives she had left behind when Lincoln was born.
After two months in the hospital, Maggie and Anthony DeLuna had brought their son home to their cramped Tampa apartment, carried him and all his machines up three flights of stairs and started the constant battle of keeping him alive.
Maggie searched for women like her, mothers with sons who might not live long.
Eventually, she came across a group of parents whose boys had the same genetic defect as Lincoln: X-linked myotubular myopathy. She learned about a national conference and a foundation raising money for research.
She reached out to the head of the foundation, another mom who lived in Florida, a woman she’d seen in the dog video: Alison Frase.
There were emails those first months of 2014, then teary phone calls that went on and on.
Alison learned about Lincoln and the curse Maggie’s family carried.
Maggie heard about Alison’s son, Joshua, who had outlived expectations and gone on to be inducted into his high school’s National Honor Society — though he almost died too many times to count. His parents spent his whole life trying to cure him.
“We’ve been at this almost 20 years,” Alison told Maggie. “So many things are moving forward right now.”
If scientists were fixing dying dogs, Maggie thought, surely they could save her son.
“Let’s just go get a cure”
Alison Rockett had helped manage the band Guns N’ Roses. Paul Frase was a defensive lineman for the New York Jets. When she was 27 and he was 26, they met by a pool table at a New York bar.
They planned their wedding for a bye week in the NFL schedule. “Jets’ Frase Rocketts to the Altar,” wrote the New York Daily News in 1991.
When their son was born four years later, he couldn’t cry or move anything but his right hand.
Doctors ruled out all kinds of rare diseases. Months went by before a lab mailed Paul and Alison the diagnosis, XLMTM, plus four pages of explanation, copied from a medical journal. Alison hadn’t known she was a carrier; no one in her family had even heard of the disorder. Only 55 other people on the planet had the disorder.
No one knew how to help. No one was even studying the condition, much less trying to cure it.
Researchers, in 1995, were focused on AIDS and helping soldiers overcome Gulf War Syndrome. Scientists were working on the $2.7 billion Human Genome Project, a 15-year effort to map and sequence DNA.
The Frases decided they had to do something.
Joshua was 6 months old when Alison wrote her goals: Find a cure, find families like mine, find my voice.
They started a nonprofit, The Joshua Frase Foundation, and called all their connections.
Alison threw a fundraiser at the Hard Rock Cafe in Boston. Paul invited football players from Syracuse University, the Jets and New England Patriots, plus friends who now worked on Wall Street. The foundation raised $144,000.
Alison would later move the gala to the Boston Harbor Hotel and sell out 450 seats. Donations doubled. The band Boston played one year, then the Red Hot Chili Peppers and later, Peter Wolf, from the J. Geils Band.
After Paul got picked up by the Jacksonville Jaguars, he and Alison moved to Florida with their fragile son. They knew they had to work fast and fund the research. But they had no idea how much money, or time, it would take.
Or who would even be willing to work on such a rare disease.
Alison’s mother, Elsie Rockett, was half-listening to CNN in 1996 when she heard a guest talk about growing skin. He and other doctors in a regenerative medicine program at Harvard had been working to build bladders and other tissues that might serve as transplant organs.
Elsie wondered if he could grow muscle for boys like her grandson.
She wrote down the man’s name: Anthony Atala. She phoned his office and left a message, telling him all about Joshua.
To her surprise, Atala called back.
He explained that from a piece of skin the size of a stamp, he could grow enough to fill a football field.
Then Alison got on the phone. “Can you help us?”
In 1997, Paul played in the Super Bowl with the Green Bay Packers, who lost to the Denver Broncos.
That same year, Google debuted, connecting scientists from around the world.
And the Joshua Frase Foundation cut its first check, to Atala’s lab, for $500,000.
Atala introduced the Frases to colleagues studying neuromuscular diseases. Those doctors connected with scientists in France who had just isolated the mutated gene that caused the disease.
Finally, Paul said, “we had something to believe in.”
Paul and Alison followed the research closely, calling scientists up to three times a week, raising $2 million more, then $6 million. They read medical journals and floated their own theories.
Could the cure come through regenerative medicine: Growing and transplanting new muscle?
Or was it gene therapy: Fixing the broken link?
They learned that scientists first described the double-helix structure of DNA in 1953. That molecular make-up transmitted genetic data. If a single gene was damaged, it could cause a range of diseases.
Science magazine reported early attempts at gene therapy in 1972, writing about researchers trying to create replacement genes. Two years later, the National Institutes of Health developed the first guidelines for gene research.
By the time Joshua was born, Nature magazine had reported successful gene therapy trials on three infants. And other forms of DNA modifications were emerging.
Scientists could slice and splice genes, or edit a single defective one.
Or they could clone a copy of a correct gene and inject it into a patient to override the broken one.
The Food and Drug Administration was just beginning to allow clinical trials for gene therapy.
Paul and Alison obsessed over the options, weighing risks and outcomes, growing impatient as their son grew weaker.
Sometimes, when Alison was ready to give up, she told Maggie, “I’d get this sign.” She would be doing dishes or folding laundry and this movie would come on TV.
In Lorenzo’s Oil, Susan Sarandon and Nick Nolte have a son with a rare disease who needs a treatment no one knows how to make.
So they set out to save him.
Joshua was 4 in 1999, when a teenager named Jesse Gelsinger, from Tucson, Ariz., died during a gene therapy trial at the University of Pennsylvania.
Almost immediately, the National Institutes of Health shut down all clinical trials involving human gene therapy: More than 2,000 potential treatments for hundreds of inherited illnesses. “It was a disaster,” Paul said.
But in universities across the world, doctors kept conducting experiments, while the Frases kept raising money.
Alison also started a registry and built a database of medical information about 410 people from across five continents. She was sure the disorder was more common than doctors thought. So many boys died before they were even diagnosed.
Joshua had a mild form of myopathy, which didn’t require a tracheostomy. With the help of a respirator pack, he could breathe a little on his own. He didn’t have to be permanently attached to a ventilator. And he could talk. “He was so funny,” Paul said. “And smart.”
By the time he was 5, Joshua could steer his wheelchair and play computer games with just his right hand. Alison home schooled him at first, then sent him to third grade.
When Joshua turned 12, he had lived a decade longer than expected. But he weighed only 67 pounds and had become too weak to sit up. So he lay on a gurney while classmates wheeled him around.
“Researchers kept saying all these papers had to be published, then peer reviewed,” Paul said. “Next month kept turning into next year.”
Joshua was in middle school, in 2007, when Alison first saw the mouse video. The Harvard researcher had sent her footage of two mice, who had been given X-linked myotubular myopathy. French scientists had treated one with gene therapy.
Alison watched as the limp mouse began to move, then, slowly, haul itself onto its feet. When it started to walk, Alison gasped. When it grabbed a wire with both front paws, and held on, she wept.
Some of the researchers her foundation was funding worked with those French scientists. In America, scientists were thinking about conducting tests on zebrafish.
The Frases wanted to move faster. They knew the government would not allow a trial on people until the procedure could be tested on large mammals.
Alison asked the researchers: “Do other animals have this same condition?”
No one knew.
At a conference soon after, one of Atala’s colleagues from Harvard, Alan Beggs, met a professor from the University of California, San Diego who was studying neurological disorders in dogs.
The professor mentioned that a Canadian vet had sent her muscle samples from a Labrador that looked like they were affected by X-linked myotubular myopathy. Some of the dog’s puppies couldn’t walk and could barely hold up their heads. By 4 months old, most died.
Beggs shared the news with Alison.
If they could breed the dog, and trace the defect through her litters, they could test gene therapy on those puppies.
So Beggs emailed the California professor. She reached out to the Canadian vet, who found the owner, who said the dog had just been spayed. All the puppies with the defect had died.
Joshua was 13 when Alison told the vet about him, and the mice, and the foundation. By then, the disease was taking a relentless toll; her son was barely able to move.
The vet agreed to help. Together, she and Alison combed the genealogy trails of Canadian Labradors, reaching out to other veterinarians who might have diagnosed wasting puppy syndrome, leaving messages for dozens of dog owners.
In December 2008, Alison got a call. The Canadian vet had found the owner of a chocolate Labrador with “floppy puppies” — on a farm in Saskatchewan, 2,400 miles from Alison’s Florida home.
The vet gave Alison the number for the dog’s owner. After five minutes of hearing her talk about Joshua, the man said: “I want to give you my dog. I want to help your son.”
Alison bought a coat, a dog crate and a plane ticket. Nine days later, she flew to Toronto in a blizzard, then transferred to a smaller plane. When she got to western Canada, everything was white and winds were whipping the air to 23 degrees below zero. A man in cowboy boots was waiting at the airport, holding the leash of a chocolate Lab, who was wagging her tail. He said, “This is Nibs.”
Joshua followed each experiment and all the emerging technologies. He read everything he could find about gene therapy and kept track of the 25 scientists collaborating across the globe.
He wanted to go to college, work in a laboratory, help figure out a permanent fix for boys like him. He wanted to be the first person to get the gene therapy. “The guinea pig,” Paul said, “in case there were any problems.”
Paul carried Joshua on long hikes through the woods. Alison pulled him in a wagon through Disney World. Joshua rode in an RV to scavenger hunts, church sleepovers, even took a tour of the White House.
“People who see me for the first time don’t know what to expect from me,” Joshua wrote on the website for his foundation. “Some people may think I’m not smart, and I drool a little too much. It’s weird, but most of the guys I see in class are the ones having a sleep marathon, waking up with drool on their chin. Just kidding! Besides having a little bit of a speech problem, I’m practically like any other 14-year-old, who loves to play video games.”
When Joshua was in eighth grade, he visited the laboratory at Wake Forest University where Atala and colleagues were researching his disease. Atala had moved from Harvard and teamed up with a researcher named Dr. Martin “Casey” Childers, who was growing tissue from dog placentas.
Alison gave Childers the chocolate Lab. Four days later, they all rejoiced when tests confirmed what everyone had been hoping for: Nibs had a canine version of the same carrier gene as Alison. “You could feel the excitement from researchers all over the world,” she said.
Childers bred Nibs with a black Lab, and Nibs had a litter of 12. Five of the females were carriers. One of the males, Little Gray Boy, couldn’t get up.
Alison showed Joshua pictures of the puppies. A few months later, she told him the gray one had died. The scientists had sent Nibs back to the farm in Canada. But they were starting a breeding colony with her puppies. Maybe soon, they could try to treat the sick males.
Joshua never got to see the next litter, or watch the YouTube video where the cured puppies run.
He died in his bed on Christmas Eve 2010. He was almost 16.
“It’s too late for my son,” Alison told Maggie in the spring of 2014. “But it might not be too late for yours.”
Click here for Chapter 3: The Boy.
Senior news researcher Caryn Baird contributed to this story.
Contact Lane DeGregory at [email protected]. Follow @LaneDeGregory.