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Photographs by Dilip Vishwanat
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Dr. Josh Rubin
LEAH BISKUP was a freshman at Nerinx High School, still feeling her way into a new, more grown-up circle of friends. When she was on the softball field, though, she was a kid again, running hard and reaching high for fly balls. Today was a doubleheader, and, at the start of the second game, she and a teammate headed to the outfield.
“My right side feels like it’s falling asleep,” Leah said, puzzled.
“Oh, that happens to me all the time,” the other player said. They parted to take their positions.
By the time the second player batted, Leah’s right side was entirely numb. Stubborn, she fought with herself a bit longer, then realized she had to go in.
She tried. But she couldn’t walk.
The coach ran to help her, assuming she’d dislocated her knee. Her head pounded. Bile rose in her throat, spewed onto the ground. She saw her dad in a blur—oh, right, he’d come to see her play—and drifted away again. Then there were strangers’ hands, urgent voices. She felt a long, sickening glide, heard a click of metal and realized she was in an ambulance.
At St. Joseph’s Hospital, a CT scan revealed a brain bleed. Leah needed to go to St. Louis Children’s Hospital, but a thunderstorm had blown in; a helicopter wouldn’t be safe. The Biskups watched the rain slam against the asphalt and waited for one of the hospital’s two high-level ambulance teams to return. Leah’s mother, Sara Biskup—a registered nurse who’d recognized neurological symptoms the minute her husband called—tried not to scream.
“They didn’t know if she would make it, so they wouldn’t let us go in the ambulance,” Sara says. “They said, ‘If you try to follow us, it will slow us down.’”
By the time the Biskups tore through the emergency-department doors, Leah, now unconscious, was on her way to the intensive-care unit. The next morning, two members of the ambulance team visited her there. They told the Biskups they’d thought—not once but several times—that they were going to lose her.
An arteriogram and an MRI suggested an inoperable tumor, but neurosurgeon Jeff Ojemann told the Biskups, “I’m not positive that’s the right diagnosis. Right now what we are seeing is a lot of blood. Let’s just hang on, see if we can get her awake.” Leah came out of the coma that afternoon. Her right side felt weak in places but within a few days was back to normal.
“They said a blood vessel had broken; it was a fluke of nature; they would keep monitoring it,” recalls Sara, her mouth twisting.
When Leah had another MRI in August, the blood was still there. “The body reabsorbs it over time,” Sara assured her daughter. In December, a few days before finals, Leah underwent a third MRI. Now there was less blood. Now the doctors could see, quite clearly, a tumor.
“We didn’t tell Leah until after Christmas,” says Sara. “It was in the innermost part of her brain—not inoperable, but Dr. Ojemann was questioning whether he could get in there and get it out safely without doing too much damage.”
Leah sailed through her finals and never even asked about the MRI results. “She felt absolutely fine,” says Sara, “so it was really hard to say, ‘OK, you have to go into this eight-hour surgery that may leave you paralyzed or with major brain impairment.’”
“The two most common cancers in children are acute lymphoblastic leukemia and brain cancers,” says Dr. Joshua Rubin, Leah’s neurooncologist at Children’s Hospital. Leukemia’s prevalence is easy to understand: During childhood, the cells that can turn into leukemia are constantly dividing to make more blood cells, so there are many, many chances for mutation to occur. Brain cancer’s prevalence is more complicated, says Rubin. Scientists are investigating the role of growth factors in the young brain, because “brain tumors peak during the first four years of life, then drop to their lowest point in adolescence.”
Leah hadn’t followed the curve.
Ojemann came out of the operating room happy; he told the Biskups he felt confident that he’d gotten all of the tumor. “My hair looked disgusting,” says Leah, who was in the hospital for almost three weeks. Sara’s big worry wasn’t her daughter’s hair: “When she woke up, she was lucid, but within a couple hours the swelling set in, and she couldn’t get the right words out.”
Hospital therapists urged Leah to practice talking and moving. “It was as if they had woken me in the middle of the night and told me to exercise,” she says.
Words came to her in slow motion, if at all. Once a straight-A student, she had to have tutors for the first time in her life. Her parents urged her to take the year off, to delay her sophomore year, but she refused. “I had finally started to fit in and figure out where I should be,” she says. “High school is so hard in that sense. I didn’t want to upset my life.”
Her mom gave up arguing. “She finished her sophomore-year requirements 48 hours before she started junior year,” Sara recalls.
Leah’s biggest complaint was still her hair—once her favorite feature, long, thick and wavy, it had been shaved for surgery, and six weeks of radiation made it fall out in spots and grow back kinky-curly, in stark contrast to the rest, which was now bone-straight. “I had an interesting hairstyle,” she says dryly.
Once a competitive diver, she retaught herself to dive that summer. Sara’s stomach clutched at every meet, but she knew her daughter thrived on challenge. Senior year went easier, as Leah’s brain caught its new rhythm and picked up speed.
But in April she started feeling tingly and numb again, starting in her hand, then up her arm—then in her foot and up her leg to half of her face.
“We were in the MRI machine immediately,” her mother says. “They said it looked fine, maybe it was post-radiation problems—but she kept having incidents."
When Leah went to her prom, her mother pulled her date aside and briefed him: “If this happens, take her to Children’s.”
He sneaked out of the dance at 9 p.m. and called Sara: “I just want you to know, everything is going OK.”
Leah graduated. Two weeks later, her family threw her a big graduation party. The living room was still cluttered with presents that Tuesday, when she came downstairs saying, “It’s in my face.” She kept talking, but the sentences came out as gibberish.
“She thought it was funny,” says Sara, the moment’s horror still in her voice. “I said, ‘This is not funny. This is serious.’”
In 1950, fewer than 10 percent of kids with acute lymphoblastic leukemia survived; today, more than 90 percent survive.
In 1950, about 30 percent of kids with brain tumors survived; today, about 50 percent survive, and most of the improvement is due to a decrease in surgical complications.
Why are brain tumors so difficult to treat? First, you can’t remove the usual “margin” of normal tissue without damaging the brain. “You scoop the tumor out and peel it away from normal issue,” explains Rubin, adding that the surgeon must count on radiation to destroy any microscopic invasive disease that’s left behind.
In the past, radiation meant using a single uniform source and irradiating huge areas of healthy brain tissue to reach the irregular projections of the tumor. Today, a computer can create a field that conforms to the shape of the tumor, allowing radiation to enter the brain from many angles, focusing on the tumor and sparing adjacent tissue.
Another obstacle that’s being overcome is the blood-brain barrier, which protects the brain from chemotherapy delivered through the bloodstream. Physicians have learned to inject drugs into the cerebrospinal fluid instead. Leah underwent several spinal taps during chemotherapy, but she refused anesthesia, insisting that she preferred a little pain to the disorientation. “I don’t want to be down any more than I have to be,” she says.
An emergency MRI showed two tumors, one in the same spot where the first one had grown and the other on the outer surface: anaplastic ependymoma. Leah’s neurosurgeon had moved to Seattle, but the Biskups were ready to fly their daughter up there until they met Dr. Jeff Leonard, on staff at Children’s, and decided they could trust him.
Before surgery, Leah fretted not about the outcome but about her hair. It was finally all the same length, although still half curly and half straight. She ordered a giant cookie and had it delivered to the scrub room, iced with “Leah’s Rules for Surgery: 1.) Watch the hair. 2.) I want the big side of the room. 3.) Watch the hair.”
A wiggly line of frosting awaited Leonard’s signature.
She made it through the eight-hour surgery and got the big side of the room—but the hair had to go. Leonard gave her the bad news himself—and it dismayed her far more than the experimental chemo he was recommending.
The chemo was as intense as it gets, and Leah experienced every side effect possible—except one. She had vowed she wouldn’t throw up, and she didn’t.
“There is a kind of tumor that, even when it is taken completely out—to the best of our ability to tell—has a tendency to come back,” says Rubin, “and when it does come back, it’s often more difficult to treat. At that point, you can’t give radiation therapy again; you make an assumption that the tumor’s resistant to radiation, because it survived and grew back.” Chemotherapy, then? For years, it had been pronounced virtually useless against childhood brain tumors. But Leah’s tumor recurred just when chemo for brain cancer was undergoing an experimental revival, and Leah had an excellent response.
In the near future, genetic science will offer more precise ways to determine chemotherapy dosage, notes Rubin. “Different people metabolize drugs differently. Some people get rid of chemo faster and probably should be given higher doses; others show more toxic effects. We’ll soon be able to do limited genetic profiles to determine dosage, identifying at the start which patients need more intense therapy to increase cure and which need less intense therapy to reduce toxicity.”
When Leah had learned she had to have surgery, her first question—after the hair—had been, “What about Marquette?” She’d been accepted to Marquette University, as had all her closest friends. But Marquette was out, at least for the first semester. Her next words? “Call SLU.”
Fragile as a paper doll after the chemo, she insisted on going to her first classes that fall. Sara drove her down to Saint Louis University, muttering objections all the way. They parked, and Leah was short of breath before she’d gone five steps.
“I saw this guy in one of those little golf carts,” says Sara, “and I said, ‘Can you just give her a ride to that building?’”
“OK, ma’am, but I don’t normally do this,” he said.
“I don’t normally do this either,” Sara replied through clenched teeth. While Leah was in class, Sara found a wheelchair. When Leah came out—pale, her wig still unfamiliar—Sara begged to take her home.
“Oh no,” said Leah. “I’m going to my second class.”
She came home having been assigned 70 pages to read in two days and was too sick to concentrate even when her mother read them aloud. “I can’t do it,” she finally burst.
“I know, I know!” her mother said, thrilled that her stubborn daughter had finally come to her senses. “I’ll call right away.”
“I was so worried they would be disappointed,” recalls Leah, “and”—the harder truth now—“that I would be disappointed with myself.”
“In the past, many children had significant damage to their brain after radiation and often were unable to lead independent lives,” says Rubin. “Today we recognize that children with memory and cognitive deficits are still capable of learning; you just have to alter the way you teach them. Leah was unable to remember what she had heard in class that day; she couldn’t retrieve the information. But she could learn and remember through repetition, practicing the information over and over until she turned it into an executive function of the brain and not a retrieval function. She went back to school with a tape recorder and listened over and over all night long.”
Leah is entering her third year at Saint Louis University, and she has made a decision she never would have predicted: She wants to become a nurse. Anatomy and organic chemistry put the decision to an immediate test last spring, and she made it through—although not without a few wails. “There are people who study a couple days,” she groans, “and I study from the end of one test to the next. It frustrates me so much. I work and I work and I work, and I get B’s. I used to put in one-eighth as much effort and get A’s!”
Last summer, she went to a young-adult cancer-survivor camp, kayaking in Colorado. She got to be good friends with a 24-year-old guy who was wearing a “Cancer Sucks” T-shirt the first time she saw him, and with a young woman, 22, from California. A few months ago, Leah learned that the young woman’s cancer had come back. She managed to graduate from college while going through chemo, and she’s about to undergo a bone-marrow transplant.
“You have the flu or a cold, you take care of it and it’s gone for the time being,” says Leah. “Obviously there’s a chance that you are going to get a cold again.” Her voice, normally bubbly and warm, sounds distant. “Lately I’ve been worried about it. After the first surgery, I was never really concerned. But in April of 2004 they said it was nothing, and two months later it was something. It’s hard for me to trust ever again that it’s nothing.”
What she’s not mentioning are the symptoms—tingling and numbness again, and horrific headaches—that have plagued her since Christmas.
“We had several emergency MRIs, all of which were fine,” says Sara, keeping her voice even. “They think now that the pain is nerve pain. She doesn’t stop, though. The other night, she had a really bad headache, and she had a test the next day, so she came home—and ended up studying two more hours before she went to bed.”
Leah shrugs. “It helps me forget about the headaches.” She has a good cry every now and then but otherwise just keeps busy. As soon as she finished her last spring exam, she started writing a book about her experience with cancer. She says that as much as she would never have wished this to happen to her, she’d never choose to undo it, because it has deepened and changed her.
When Sara suggested acupuncture for the headaches, though, the dam burst: “Geez, Mom, don’t you think I’ve been through enough? Do we have to have needles?”
pulling out all the stops
Researchers at Washington University helped break the genetic code, and physicians at Children’s Hospital are determined to use the knowledge as quickly as possible. They are partnering with the Washington University School of Medicine and waging one of the largest fundraising campaigns in St. Louis history, a $125 million drive to launch a $355 million Children’s Discovery Institute.
“In the past, Washington University didn’t want Children’s raising money on its own and competing, and Children’s didn’t want to raise money that wouldn’t go to the hospital—the usual angst,” says Dr. Jonathan Gitlin, director of genetics and genomic medicine at Children’s and a professor of pediatrics at the medical school. “It wasn’t as bad as a cartoon of Mohammed in the Muslim world, but there was some consternation.” They worked through it, letting the idea of accelerating cures for childhood disease dissolve the politics. Together the two institutions forged a plan focusing on four areas where collaboration could really make a difference.
“The leading medical cause of death for children is congenital heart disease,” says Gitlin, “and another leading cause is cancer, especially pediatric brain cancers.” Those diseases went to the top of the list. (Rubin and his colleagues are already talking about a different way of attacking brain cancer, using chemotherapy to stop the growth of blood vessels that feed the tumor.)
Third on the list were lung disorders (from cystic fibrosis to asthma), and musculoskeletal disorders came fourth.
Instead of awarding grants to individuals, the Children’s Discovery Institute will “leverage the strength of the university and bring together people who would not otherwise be working on these problems,” says Gitlin. “One of the most brilliant women in nanotechnology—the science of making very, very tiny machines, the size of cells, that can sense microscopic proteins and viruses in your blood—is in chemistry at Washington University, but she has never thought about congenital heart disease. In business, they call this ‘thinking outside the box.’ And Washington University is one of the few places where it can really happen, because there is so much talent.”
