Pre-implantation genetic diagnosis offers hope but prompts ethical concerns

BY ESTHER LANDHUIS

It's not science fiction. Nowadays prospective parents can not only know the sex of their unborn child but also learn whether it can supply tissue-matched bone marrow to a dying sibling and whether it is predisposed to develop breast cancer or Huntington's disease -- all before the embryo gets implanted into the mother's womb.

"What I think the public doesn't understand is that this technology is not in the distant future," said Stanford law Professor Hank Greely, kicking off a Feb. 27 conference that explored the controversial topic at the crossroads of human genetics and reproduction: pre-implantation genetic diagnosis (PGD). Presented by the Stanford Center for Law and the Biosciences, a new program directed by Greely, the conference drew more than 100 people to hear a panel of eight nationally known law professors, bioethicists and biomedical research scientists discuss whether California should regulate PGD.

The verdict, more or less, was twofold: Track PGD's safety and success with greater vigilance, and use the technology to prevent disease but not to seek perfection.

Pioneered by British physicians in 1989, PGD is an extension to the previously developed procedure, in vitro fertilization (IVF), in which eggs are removed from a woman's ovaries and fertilized in the laboratory with sperm. Three days later, when the resulting embryos have grown to the eight-cell stage, the doctor can pluck a single cell from each embryo and use PGD to screen the cells for specific genetic defects and chromosomal abnormalities. One to four desirable embryos will be transferred into the woman's uterus for development.

To date, specialists have performed over 6,500 cycles of PGD worldwide, and 1,000 children have been born from the technology over the last decade.

PGD can monitor about two-dozen disorders with specific gene culprits -- including cystic fibrosis, sickle cell anemia, muscular dystrophy, Tay-Sachs disease and Fragile X syndrome. Newer techniques also have enabled PGD to detect chromosomal aberrations that cause Down syndrome and certain blood cell disorders.

Though these tests -- which cost $2,500 to $4,000, on top of the $6,000 to $12,000 for IVF -- are most commonly used by couples with infertility or high maternal age, they have become particularly enticing to families with previous children born with genetic disorders. "No one wants to walk the pathway of throwing genetic dice and hoping they come out the right way," said Mark Hughes, a molecular geneticist at Wayne State University in Detroit who helped pioneer the field of PGD for couples at high reproductive genetic risk.

But just because we have the technology doesn't mean we should always use it, Hughes said. The public seems to agree.

According to a 2002 survey conducted by the Genetics and Public Policy Center at Johns Hopkins University in Baltimore, more than 70 percent of the 1,211 respondents nationwide approved the use of PGD to avoid serious genetic disease. However, less than 30 percent favored using the technology to choose a child's sex or other desirable characteristics, such as strength or intelligence.

For a childless couple with no history of chromosome X-linked genetic disorders, the use of PGD for sex selection may seem a mere luxury. On the other hand, many may feel justified in applying the technology toward "family balancing" -- for a family who wants a son after having five daughters, for instance.

However, though family balancing sounds reasonable enough, it could easily be construed as a violation of equal rights protection under the U.S. Constitution, argues Radhika Rao, a professor at the University of California-Hastings College of the Law. Rao said it would be difficult to legislate the use of PGD for sex selection without the appearance of granting undue favor to couples with many children. "The problem with contextual decisions is that they can lead to discrimination," Rao said.

In the early 1990s, couples began to inquire about using PGD to select embryos that would produce a tissue-matched child whose blood could be used to cure a sibling's fatal immune disease.

While over two-thirds of the 2002 survey respondents approved the use of PGD for this purpose, some experts fear that "savior siblings" could be instrumentalized as a means to the parents' end. Rebecca Dresser, a Washington University law professor and member of the President's Council on Bioethics, raised this concern at the conference and cited a council report that will be released in about a month. "How will the donor child be regarded by the family, especially if the transplant fails?" Dresser asked.

John Robertson, a bioethicist at the University of Texas-Austin School of Law, dismisses this worry. He argued that couples who are willing to endure such costly and involved procedures as PGD and IVF for the chance to save an ailing child are surely committed to being good parents to subsequent children.

Another concern raised in the upcoming council report stems largely from the cost issue. Since PGD is expensive and not covered by insurance, some fear that its widespread use could further stigmatize disabled people and increase the gap between "haves" and "have-nots."

But what really makes people cringe, perhaps because it is the least tangible of fears, is the possibility that PGD could one day be used to not only avoid genetic diseases but also select for desirable traits, such as athletic prowess or musical ability. "Designer babies might be possible from a technological perspective, but biology is going to prevent it from happening," said molecular geneticist Hughes. Most of these traits are controlled by multiple genes, making the odds of creating an embryo with the "optimal" gene combination nearly impossible from a statistical standpoint.

"When it comes to public policy, we have to talk about what's reasonable in the near term," Hughes said.