updated 02/12/2001 AT 01:00 AM EST
•originally published 02/12/2001 AT 01:00 AM EST
She then plants loud smack on the baby's cheek with an earnestness that suggests something deeper than simple sisterly affection. In truth this lively Denver first grader, whose brown hair is just now growing in after the ravages of chemotherapy, quite literally owes her life to Adam, just four months ago Molly, born with an aggressive form of Fanconi anemia, a rare and fatal blood disorder, was saved by a remarkable new procedure in which she received blood from her newborn brother's umbilical cord as a means of regenerating her own diseased bone marrow and failing immune system. While such transplants are relatively rare, Molly's case was noteworthy for yet another reason: Adam was not only conceived in the hope that he could save his sister's life but he was selected as a perfect donor when he was just an eight-celled embryo in a laboratory test tube.
The case of Molly Nash marks the first time that, through a combination of pioneering medical and genetic technologies, a specifically selected test-tube baby has saved the life of another human being. As such, it may have far-reaching implications for the treatment of thousands of children suffering from otherwise incurable inherited genetic disorders. Yet despite its miraculous results, Molly's story has also sparked controversy among critics who fear that such procedures raise the specter of genetically engineered "designer children" whose traits could be determined by little more than a parent's whim. "If we think it's okay for a parent to select characteristics in a child to avoid a lethal disease, how can we not approve of a parent saying it is useful to have a child with athletic ability or one who is tall?" says Alex Capron, codirector of the University of Southern California's Pacific Center for Health Policy and Ethics. "Where you get to the slippery slope is when a baby becomes a useful commodity."
Not surprisingly, Molly's parents took a purely pragmatic approach to that knotty philosophical problem. "Give me an ethicist who wouldn't do the same thing if he had a child in Molly's situation, and I'll talk to him," says Lisa, 34, a neonatal intensive-care nurse. Adds her husband, Jack, 36, manager of a Denver hotel: "We had always wanted more kids from the beginning. And we wanted to save Molly's life. It's as simple as that."
But on the morning of July 4, 1994, as Lisa was giving birth to her first child, nothing seemed simple at all. "Molly came out and everyone started yelling," she recalls of the delivery. "I didn't even get to see her. They just whisked her off." Later, doctors gave the Nashes a grim report. Molly had been born without thumbs and with deformed forearms. She had two holes in her heart, was deaf in her left ear, was missing hip sockets and had an abnormally small head and eyes. Poring through a copy of Smith's Recognizable Patterns of Human Malformation, Lisa found the disease whose symptoms seemed to match her baby's. "When I turned to the page about Fanconi anemia," says Lisa, "there was a picture of the small face, the small eyes. I knew right then and there."
In time the Nashes learned that Molly's best hope was a cord-blood stem-cell transplant, in which a patient first undergoes radiation and chemotherapy to rid the body of diseased cells. Blood from an umbilical cord, which contains high concentrations of cellular building blocks called stem cells, would then be infused directly into her bloodstream in hopes of reviving her defective bone marrow—the substance that produces the body's blood supply, including disease-fighting white blood cells. But there was a major stumbling block. Even today, stem-cell transplants have been successful in only 20 percent of all Fanconi anemia cases, odds which increase to 85 percent when the donor is a sibling. Although the Nashes had always wanted more children, the idea of producing another child with Molly's disease was unthinkable. "How could we have another child," says Lisa, "when there was a l-in-4 chance of this happening again?"
But the Nashes found cause for hope in 1995 when they met with Dr. John Wagner, scientific director of clinical research of the Blood and Marrow Transplant Program at the University of Minnesota in Minneapolis. He told them about a new procedure called preimplantation genetic diagnosis (PGD), in which embryos conceived in a test tube could be screened safely at a remarkably early stage to determine their suitability as donors.
Wagner referred the Nashes to a doctor who, using the father's sperm, was fertilizing as many as 20 of the mother's eggs at a time. Then, when the embryos were at the eight-cell stage, a single cell was removed and screened for genetic abnormalities, including Fanconi anemia, without damaging the embryo. Crucially, the cell could also be tested for its human leukocyte antigen (HLA), the key factor in determining donor compatibility. Only disease-free embryos that were also a genetic HLA match would then be implanted in the mother.
In 1995 the Nashes underwent PGD for the first time, but Lisa did not become pregnant. Meanwhile, because of Molly's compromised immune system, she led a highly restricted existence. She was home-schooled, seldom had play dates and was kept from the park or playground when other children were there. In her rare ventures outdoors she wore a surgical mask, as she did one day at the age of 3, when Lisa allowed a friend to take her to a local dance studio. Molly was so enthralled that the teacher, Debbie Stark, offered to hold special classes for her with just three other students. "We just decided that we couldn't keep Molly away from everything," says Lisa.
Despite the precautions, Molly's condition grew worse. By 1997 her bone marrow was failing, and the following year she showed signs of preleukemia. "Once Fanconi patients develop leukemia, it's very hard to cure them even if the transplant is successful, because the leukemia will often recur," says Dr. Wagner. "I told the Nashes, 'We're running out of time.' "
So, two months after Molly's fourth birthday, a Denver in vitro specialist, Dr. William Schoolcraft, sent the Nashes to Dr. Charles Strom at Chicago's Reproductive Genetics Institute, which specializes in PGD. In January of 1999 they tried the procedure again, but Lisa miscarried at five weeks. Twice more their attempts failed. But nearly a year later, on their fifth try, one of the couple's 12 embryos was found to be not only an HLA match for Molly but free of Fanconi anemia and robust enough to be implanted. On Dec. 24, Lisa took a pregnancy test at Dr. Schoolcraft's office, and that afternoon received a phone call. "When he told me it was positive, I started to cry," she says. "I said, 'You're just telling me this because it's Christmas Eve.' Then I called Jack at work and told him, 'You're gonna be a daddy.' "
As Lisa's pregnancy progressed, Molly's health declined. "She would get worn out. She'd say, 'I'm tired,' " says Jack. "And that wasn't like her." But when one medical professional asked if Lisa might consider inducing labor to have her baby delivered sooner, she said, " 'You know what? Adam was brought here to be Adam.' I wasn't going to compromise and have him born prematurely, with all the problems that go with that."
Finally, on Aug. 29, following a 52-hour labor, a healthy 7-lb. 7-oz. Adam Nash was born by C-section. Immediately following the birth Dr. Strom supervised collection of the cord blood while it was still attached to the placenta. Then Jack's father, Manuel Nash, 66, a real estate investor, carrying a container of the blood, left on the first available flight to Minneapolis, where Dr. Wagner tested then froze the blood in anticipation of Molly's transplant.
A few weeks later, after the Nashes arrived at the Bone Marrow Transplant Unit of Minneapolis's Fairview-University Medical Center, Molly began her pretransplant regimen: four days of chemotherapy, full-body radiation and the beginning of a two-month course of an antirejection drug. Then, at 1:30 p.m. on Sept. 26, in room 4A at the center, she underwent the simplest yet most crucial procedure of all. With her hair still showing traces of the pink and blue dyes that she and her mother had washed in as a lark two days before, Molly sat on a hospital bed as a nurse wheeled in an IV cart and a 4½-oz. bag of Adam's cord blood, which she attached to a tube leading directly into Molly's heart. For the next 45 minutes, as Molly cradled her little brother in her lap, Adam's blood flowed into his big sister. "We all cried, except Adam," says Lisa. "It was a culmination of six years of waiting and hoping and wondering for a chance for Molly to have a normal healthy life."
But not right away. Within days Molly began to suffer from diarrhea and vomiting, hemorrhaging in her eyes and sores in her mouth—all side effects of chemo and radiation. "We didn't know how sick she'd be," says Jack, who along with his wife stayed by Molly's side as her shoulder-length hair fell out and more than a dozen children and adults in the transplant unit died one by one. "I hung a blanket over the window of her room," says Lisa of that mournful period, "like I was warding off the evil spirits."
But suddenly, 18 days after the procedure, "I got up and started dancing again," says Molly. "It was to Ricky Martin on the radio. I said, 'Mommy, let's dance.' And we danced." Lisa well remembers the moment. "I knew she was still Molly then, and I cried." Twenty-two days after treatment a biopsy showed that Adam's immune system had indeed taken over in Molly. "That," says Jack, "was my moment."
By early last month, says Dr. Wagner, Molly's bone marrow was nearly normal. "I have never seen it recover at this pace before," he says. Now, four months after her transplant, Molly lives with the residual effects of her ordeal. Surgery has only partially corrected her hand and arm deformities, radiation has rendered her sterile, and she may run a higher risk for certain forms of cancer later in life. Still, while she will have a somewhat compromised immune system for as long as a year after her transplant, there have been no signs that her body is rejecting its transplanted cells, and doctors expect that she will lead a long and normal life. In fact, they have high hopes that her case may contribute to their knowledge of leukemia, bone marrow failure and other life-threatening diseases. "Our motivation all along was, 'How can we make it better for Molly?' " says Dr. Wagner. "But in the end, a lot of people may benefit."
At the moment those lofty considerations are not a high priority at the Nash house, where Molly is busy planning her immediate future. "I'm going to do fun stuff," she says, cuddling her baby brother. "I'm going to go to school. I want to ride the school bus, and my dance teacher said I could take as many classes as I want, so I'm signing up for nine."
And while she has not forgotten the remarkable medical procedure that she has just undergone, she does seem to have put it into perspective. "The good part about the transplant," says Molly, "was coming home."
Meg Grant in Minneapolis and Denver