Rebecca Lilly
James A. Parcell--The Washington Post

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Rebecca Lilly, of Takoma Park, is the first child treated with gene therapy for brain cancer.

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Can Gene Therapy Save Her Life?

I

'm soooo sick of Barney," groaned Rebecca Lilly, eyeing the feel-good purple dinosaur on TV in the waiting room at Children's National Medical Center.

Fifteen-year-old Becca was about to undergo brain surgery for the third time since her cancer was diagnosed in 1991. As before, surgeons would open her skull and cut out as much of the tumor as possible. But this time they would also try a radically new attack.

This time they would inject into her brain an altered virus carrying a gene designed to trick the tumor into committing cellular suicide.

A

nurse checked Becca's blood pressure and warned her that "when you wake up there are going to be tons of people all around you -- that's normal."

At 9:40 a.m., neurosurgeon Steven J. Schiff told the Lillys he wanted to get started. Down the hall, Becca waited for the pre-anesthesia line to go in. She looked away and grimaced, her left hand gripping her dad's, as the needle-tipped tube slid into a vein in her right wrist. Done. Becca trundled off toward the operating room, escorted by the anesthesiologist.

Her parents, Joe and Maureen Lilly, huddled briefly with Schiff in the hallway. He explained that he would remove as much tumor as he could, but probably wouldn't get it all. He also had to keep an eye on the time. The crucial gene therapy cells, on their way by courier from a laboratory freezer in Gaithersburg, would stay fresh only until 2 o'clock.

"The main thing she's worried about is the haircut," Maureen Lilly said. She had promised Becca she'd mention this. Schiff nodded knowingly and smiled. "I've been through this many times."

He shook hands with the Lillys and headed for the operating room.

Becca's parents embraced. Her mother was crying.

B

ecca Lilly, a 10th-grader at Good Counsel High School in Wheaton, has a cruel disease. Even its name sounds scary: glioblastoma. The most aggressive of brain tumors, glioblastomas grow back even when treated with state-of-the-art medicine -- surgery, radiation and chemotherapy. Of children diagnosed with a glioblastoma, only one in five is alive three years later.

Becca's tumor was discovered more than four years ago. It was treated with surgery and radiation in 1991 -- and again in 1994. When the tumor showed up for a third time last November, standard medicine had nothing more to offer her.

Rebecca holds her dad's hand as she gets
ready to go into surgery.
James A. Parcell--The Washington Post

By coincidence, the same week her cancer came back, doctors won final approval to test a dramatic new approach to pediatric brain tumors. The experimental treatment, a form of gene therapy, will be tried in 15 children at Children's and three other medical centers. The research is paid for by Genetic Therapy Inc., the Gaithersburg biotechnology company that engineers the gene therapy cells and holds exclusive marketing rights to the technology.

"We never bypass conventional treatment for something experimental," said Roger J. Packer, chairman of neurology and director of the brain tumor program at Children's Hospital. "But in Becca's case, she didn't have any standard treatments left."

No one knows if it will work. But in order to find out -- or even to learn the next step toward an answer -- doctors must test a promising but unproven therapy on patients. Someone must go first. Ethically, the only patients eligible are those who face such a dire prognosis with known treatments that they have nothing to lose by risking the unknown.

W

hich is why, on the morning before Thanksgiving, Becca was in surgery again at Children's Hospital. Packer didn't dare wait until after Thanksgiving. The tumor had doubled in size since August.

Operating Room 3 was bustling toward surgical readiness. Thirty-six glossy black-and-white negatives of Becca's brain were lit up on one wall.

Becca lay unconscious, her auburn hair hanging over the edge of the operating table, while neurosurgeon Schiff shaved her left temple. The amber disinfectant mixed with her hair like shampoo.

The first hint of trouble for Becca had come in May 1991, two months before her 11th birthday. She started having fierce migraine headaches.

Schiff let the surgical team know he was feeling time pressure because of the short-lived gene therapy cells, which had been prepared that morning. "I want this out before the cells die," he said firmly. There were 14 people in the room.

Schiff popped a CD into the portable Sony. By operating room etiquette, the chief surgeon gets to choose the background music, and Schiff chose Bach's cello suites -- music he loves "but not enough to be distracted by it."

The gene therapy cells had arrived, a tiny vial of cloudy liquid in a white Styrofoam cooler. Debbie Lafond, the gene therapy project's chief nurse, checked the label and announced that the cells were good until 1:08 p.m.

"What!" exclaimed Schiff. He was stunned. He had understood that he would have three hours. It was already past 11, and the cells would be dead in two hours.

L

afond explained that the cells had been thawed and sent early to beat rush hour traffic in the freezing rain.

"That doesn't help us," Schiff said. "They made 'em too early."

He looked at the clock. There was no way he could have the tumor out within two hours, he told Lafond. "Tell 'em to make up another batch and shuttle 'em down here as fast as they can."

Becca was out of sight, draped in blue-gray surgical sheets and buckled in with a Velcro lap belt. Sixteen tubes and wires led to her from a soda machine-sized bank of pumps, dials and digital monitors on her right. An oval porthole in the surgical drapes exposed the upper left side of her head -- glistening and bald.

Schiff and senior neurosurgical resident Ghassan Bejjani cut a sickle-shaped flap of scalp above her ear and folded it forward. Gloved hands moved efficiently back and forth over the surgical field, cutting, suctioning, clamping, electrically sealing off blood vessels.

B

rain surgery like Becca's requires five incisions: first the skin, then the muscles, the skull, the leathery protective membrane called the dura mater -- and finally the brain itself. It took the surgeons more than two hours just to get a look at the tumor.

They had to drill through the skull without tearing the membrane underneath, and then move that membrane out of the way to get at the tumor -- all without disturbing the brain and its blood supply. It is painstaking, intricate, bloody work. "There's no way to rush," Schiff said.

A surgeon removes a tumor from Rebecca's brain.
James A. Parcell--The Washington Post

Becca's previous treatments made it all the more difficult. The skull incision from her earlier surgery had been reinforced with three small titanium plates, shaped like snowflakes and screwed into the bone.

Schiff dislodged a jagged-edged disk of skull, a small saucer of bone, and set it aside in a bowl of antiseptic solution. Now the only thing between the surgeons and the tumor was the brain's outer membrane, hardened with scar tissue from radiation. "Like cement," Schiff said. He paused occasionally to inspect the ultrasound image of Becca's brain on the computer screen beside him. The tumor was a small bright spot amid a pulsing mass of shadowy gray clouds.

In all, Schiff would remove about a cubic inch of cancer, but it was not a neat block or lump. It was countless bits of mushy, ragged tissue. "These tumors have fingers, and they grow into the brain," he said. "That's why surgery can never get it all."

Nearly three hours into the operation, Schiff used forceps to lift out the first specimen of tumor, a wad of gray like the end of a Q-Tip. He sent it downstairs to the pathology lab, where it was quick-frozen, razor-sliced and examined under a microscope to make sure it was cancerous -- not merely scar tissue in disguise.

Suddenly, it felt like a surgical halftime, a lull while the surgeons waited for the pathology report. Because of a backlog in the lab, that took far longer than expected. The anesthesiologists kept watch over the patient, who otherwise seemed oddly abstract. The open wound in her head pulsed with each heartbeat.

B

etween 1,500 and 2,000 children develop brain tumors each year in the United States. Some 20 percent have the kind of tumor Becca has.

The first hint of trouble for Becca had come in May 1991, two months before her 11th birthday. She started having fierce migraine headaches. Occasionally she'd get spacey, eyes glazing and her speech a little "off."

Then one evening she blacked out with a seizure. Her parents called an ambulance, and she wound up at Georgetown University Hospital for three days of inconclusive tests. A magnetic resonance imaging scan, or MRI, showed a little spot on her brain. The doctors thought at first it was a migraine that had hemorrhaged.

The spot grew. The surgeons confirmed that it was a brain tumor and took out what they could. Radiation followed to slow down the rest.

That held the tumor in check for nearly three years, until June 1994, when Becca underwent surgery again at Georgetown. But two months later, an MRI showed still more tumor growth. She went to Boston for experimental radiation treatments, and the waiting began anew.