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Can Science Help You Design a Child?.

From the WebMD Archives

Oct. 6, 2000 -- Almost everyone has sometimes wished they had a trait they lack -- maybe being two inches taller, or blue-eyed instead of brown-eyed, or musically talented. In the future, this type of desire could be more than wishful thinking. It's not so far-fetched to think that doctors might someday be able to actually create certain traits in our offspring through genetic manipulation.

After all, scientists already are starting to cure diseases by inserting certain genes into people to fix the defective ones that cause abnormalities. Researchers also genetically engineer mice, rats, and other animals that they use to study illnesses: They have created fat rats to study diabetes and mice with the immune deficiency disease lupus in an effort to find treatments and cures for these disorders.

But controversy surrounds both human gene transfers and gene therapy, with scientists, theologians, ethicists, and the man on the street wondering how far we can and should go in changing a person's genetic makeup.

The debate heated up this week, when the Fox Network debuted a show based on the premise that a secret military plot created children who were genetically enhanced to have super vision, astounding strength, catlike reflexes, and supernatural hearing.

And, as if to demonstrate that such ideas aren't necessarily fantasies, a real-life, 6-year-old Colorado girl recently got a transplant of cells to help replace her diseased bone marrow -- from her 4-week-old brother, who was cleared as a donor while still an embryo. The boy, conceived through in vitro fertilization, came from an embryo that doctors had determined was free of the inherited disorder that plagues his sister.

So in the future, will you really be able to choose your child's traits before he or she is born?

Scientists tell WebMD say that although gene therapy is still in its infancy in curing diseases, it is possible that someday, some traits could be introduced into fetuses. Still, there are serious obstacles to this practice -- including a multitude of unknowns.

"We can already do surgery on fetuses, and we have changed traits in mice embryos," says Andrew Zinn, MD, PhD, a researcher with University of Texas Southwestern Medical Center's Eugene McDermott Center for Human Growth and Development. "So it's very feasible we could do gene therapy on human fetuses, but we don't know how this would affect their development. We could probably do this to cure some diseases.

"We could probably even do this for genes for things like being a good swimmer or having blue eyes, but we don't know the genes for these things yet and it will be a long time before we do."

Malcolm Brenner, MD, PhD, director of the Cell and Gene Therapy Center at Baylor College of Medicine in Houston, agrees. "Right now, scientists are working on single-gene diseases, such as severe combined immunodeficiency disease," he says. This is the so-called bubble boy disease; children who have it must be confined to a sterile environment to protect them from potentially fatal exposure to even the most minor germs. Doctors in France have now apparently cured five such children through gene therapy, using a normal immune-system gene to infiltrate the children's own defective immune systems.

Even if before-birth genetic manipulation does become a reality, Inder Verma, PhD, tells WebMD he doubts it will become widespread -- in part because it would likely go the way of all fads.

"We could probably inject a gene that would enhance performance. But if everyone had blue eyes and blonde hair, [those traits] wouldn't stand out anymore," says Verma, American Society of Gene Therapy president and a Salk Institute for Biological Studies genetics professor. "If everyone looked like Michael Jordan, would anyone want to look like Michael Jordan?"

And while Verma, Zinn, and Brenner all agree that someday it may be possible to change the genetic makeup before birth, they all say there are technological hurdles to overcome first.

"You need a vector, something to carry the gene to the right cells [such as a virus]," Brenner tells WebMD. You need the right gene. You need to know how the cell will behave when the gene enters it. "

Further, "you need to target a specific place in the cell so the gene doesn't interfere with the normal cell function," he says. For instance, he says, if a gene is injected to protect normal cells from a cancer drug, then that gene must be delivered only to the normal cells. If it's delivered to the cancer cells, then the drug has no effect on the cancer.

These problems have been major stumbling blocks in gene therapy. The vector now most often used to carry the gene is an adenovirus. These viruses usually cause mild, upper-respiratory infections such as colds but can be altered so they won't introduce the illness. Then the adenovirus must have a delivery system. The most common method now is to inject the gene into a muscle or the bloodstream. But too much of the adenovirus can go to the wrong cells, especially the liver, where it can cause damage.

Researchers at University of Texas Southwestern Medical Center (UTSW) in Dallas recently reported a promising transport system that can be targeted to specific cells. They used an adenovirus to package the gene -- in this case, one to repair the heart. Then, they attached the virus molecule to a "microbubble" -- a bubble tiny enough to maneuver through a vein -- and injected it into the veins of rats. The investigators used ultrasound to burst the bubble when it reached its target in the rodents' hearts, successfully delivering its payload.

"This gives us the flexibility of putting the gene in a specific anatomical location," says Ralph Shohet, MD, an investigator with UTSW's Frank M. Ryburn Jr. Cardiac Center. "The problem with just injecting an adenovirus in a vein is you don't know where it's going."

With an effective delivery system, scientists believe both genetic therapy and preimplantation selection can be used to keep children from being born with defects and diseases. Preimplantation selection is when an embryo in a lab dish is chosen on the basis of whether it is free of genetic defects, then placed into the mother's womb for development.

Says UTSW's Zinn: "I think we could do gene therapy for cystic fibrosis in about 10 years; I wouldn't be surprised if someone did it in five."

As to the controversy on whether this should be done in reproductive cells, called "inheritable genetic modification," Zinn says any such effort would have to be done with great caution. "Many people liken this to playing God," he says. "We certainly don't want to do it before we know the full consequences. What if, in eliminating the cystic fibrosis, you make people and their descendants more susceptible to other disorders?"

But he says, if scientists know all the genes involved and the consequences, how could anyone argue against genetic modification that would eradicate a susceptibility to, say, diabetes or heart disease? Salk's Verma says gene therapy will likely become widespread for diseases that can be permanently cured.

Regardless, both Zinn and Brenner say that preimplantation selection is likely to be increasingly used.

"I don't see a reason not to use selection if you can cure a disease," says Brenner, commenting on the Colorado family's case. "You'll have just as many successes as failures with both selection and gene therapy. And if it cures a disease, it doesn't seem very evil to me. It seems to me it's of benefit to everyone."

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