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Six-year-old Molly Nash's newborn brother, Adam, is free of her terrible genetic disease. And thanks to a novel marriage of biotechnologies, he also will provide the cells that may save her life.
Last December, his embryo was chosen from among six because he didn't have the same genetic mutation as Molly, and because he would be a good transplant match.
Now, a month after his birth, doctors at the University of Minnesota will use blood cells from his umbilical cord to replace Molly's defective bone marrow. The procedure will give her an 85 percent chance to defeat the disease, which, untreated, causes leukemia.
It is believed to be the first time genetic testing has been used by parents to have a child who not only is free of the disease, but also is the best tissue match for a sibling who needs a transplant.
"We wanted a healthy child," said Lisa Nash, of Englewood, Colo. "And it doesn't hurt him to save her life."
Jack and Lisa Nash decided to make their story public, in an interview Monday and at a news conference today, because the technology offers hope for other families facing such genetic dilemmas. It also raises questions about the power parents now have to choose which genes to pass onto their children.
"We've crossed the line that quickly goes to 'Let's select things that we as parents want - height or musical ability,'" said Jeff Kahn, director of the university's Center for Bioethics. "That's the moral difficulty."
It is widely considered ethical to screen embryos for devastating genetic diseases, he said, because that's clearly in the best interest of the child-to-be.
However, the Nashes' son, Adam, also was chosen for traits that would benefit someone else - his sister.
University officials and physicians said they think it's an appropriate use of the technologies. In fact, the Nashes are the first of about a dozen families with genetic diseases working at the university with Dr. John Wagner to complete the expensive and arduous process that involves in-vitro fertilization and genetic testing.
A very rare condition
Molly Nash was born with an extremely rare disease called Fanconi anemia. It affects only about 1,000 people in North America, said Arleen Auerbach, an associate professor and expert on the disease at Rockefeller University in New York. In the general population, about one in 200 people are recessive carriers, meaning that the disease affects only those who inherit a mutated gene from each parent. It is far more common among people of Eastern European Jewish descent, among whom about one in 80 are carriers.
Molly, said her parents, had all the conditions typical of the disease. She was born with no thumbs, a condition largely corrected by surgery that turned one finger on each hand into a thumb. She has no problems with dexterity and uses scissors and a computer mouse.
She had no hip sockets. To correct that, she spent much of her infancy in a brace that weighed more than she did. But on Monday, she ran through Camp Snoopy at the Mall of America in Bloomington with the reckless abandon of any 6-year-old.
She has gastrointestinal problems that play havoc with her appetite. She can polish off four hot dogs in a sitting if she wants to, said Lisa Nash, and then may refuse to eat for weeks. As a result, "she uses food as a control mechanism," her mom said. To avoid the endless worry and battles, her parents had a feeding tube inserted in her stomach. Now they can provide the nutrition she needs, and she can eat when she wants to.
The one characteristic they can't cope with is her inability to make bone marrow - and the resulting leukemia that would kill her. An estimated 98 percent of all people with Fanconi anemia have bone-marrow failure by age 35, Wagner said. Half of them experience it by age 7.
The best treatment for the disease, and a common one for all leukemias and a number of blood and immune system disorders, is a bone-marrow transplant. In recent years, research has shown that umbilical-cord blood can do a better job than adult bone-marrow cells, especially for children, who can get by on the smaller volume of transplanted cells. Like bone marrow, umbilical-cord blood contains stem cells, which manufacture blood cells in the body. But it has some important advantages, Wagner said - it is free of viruses, and it comes from an infant with an immature immune system, so the recipient's body is far less likely to reject it.
A transplant also is far more likely to work if the blood cells come from a sibling, Wagner said, again because the patient's immune system is more likely to accept them. In Fanconi anemia, survival rates are 31 percent if the transplanted cells come from an unrelated donor. The rate leaps to 85 percent if the donor is a sibling.
But just as the children of parents who are carriers of genetic diseases have a one-in-four chance of inheriting the disease, children also have only a one-in-four chance of inheriting the traits that make them a good match for a sibling, Wagner said.
Without medical technology, the Nashes had only an 18 percent chance of having a child who was both free of the disease and a good tissue match, Wagner said.
"We could not knowingly bring a child into the world with that disease," said Lisa Nash. Although amniocentesis can detect the problem, the Nashes were not willing to have an abortion at 23 weeks. Lisa Nash works as a neonatal nurse, and frequently has cared for infants born at 23 weeks.
"It's a baby at that point," she said.
Making, testing embryos
When Molly was about 18 months old, they heard from Auerbach that the technology existed both to genetically test for the disease and to provide the blood cells for Molly. The procedure is called pre-implantation genetic diagnosis (PGD), and for most of the parents Wagner deals with, "it's an easy decision," he said.
It starts with in-vitro fertilization, in which the mother takes drugs to generate several eggs at once, which then are fertilized by the husband's sperm in a petri dish. The PGD takes place when the embryos reach the eight-cell stage, usually within a day of fertilization. One cell is removed, which does no harm to the developing embryos, and its DNA is examined for the chosen genetic traits. Only the embryos that are found to be free of the disease and are good tissue matches are implanted in the mother's uterus.
The Nashes went through the process five times before Adam was born. Their insurance plan, like most, did not cover the in-vitro fertilizations or the genetic testing.
About 500 children have been born worldwide, half of them in the United States, after being tested for genetic diseases while embryos, said Yury Verlinsky, director of the Reproductive Genetics Institute in Chicago, one of about a dozen U.S. clinics that do PGD. It conducted PGD for the Nash family. No Minnesota clinics perform the procedure.
Verlinsky's clinic has done the genetic screening for transplant matches for many families with disorders treatable by cord-blood transplant, but so far only the Nashes have had a successful birth.
PGD is also used to screen for such other genetic diseases as cystic fibrosis, Huntington's chorea, sickle-cell anemia and Tay-Sachs disease.
Whether PGD will be used for other kinds of genetic screening is an open question, Kahn and Wagner said, but it is already clear that parents are starting to ask.
Wagner said he has already fielded this question: Would he do a cord-blood transplant from an infant chosen as an embryo solely because it would be a good transplant match?
So far, he said, he has always answered no.
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