Prenatal whole-gene sequencing raises thorny ethical questions

(U.S. National Library of Medicine)

Someday, a pregnant woman is going to walk into the office of a doctor or genetic counselor, and plop a thick folder on the desk. The contents will be the entire genome of the fetus the woman is carrying -- every gene and chromosome -- and the parent-to-be will ask what it will all mean for the baby she is about to have.

The sequencing will provide information on what the child will be like and in some cases, what will happen during the teenage and adult years. All it would take is a simple blood test.

If parents don’t like the results, options can include abortion or maybe genetic manipulation.

The test, what scientists call prenatal whole genome sequencing, eventually will cost less than $1,000, according to experts. Perhaps millions of people will think it a good investment. A huge industry will likely grow up around it.

While it sounds like something out of the film Gattaca, the technology is not science fiction. During pregnancy a small amount of fetal DNA enters the mother’s bloodstream. A blood sample is drawn from the woman’s arm and the fetal blood is extracted and the genetic structure sequenced. This already is common in commercially available tests for specific diseases.

We are not quite there yet -- sequencing still costs thousands of dollars although the price is dropping -- but the practice seems inevitable and experts say there is no way it will be uncontroversial. Indeed, bioethicist Arthur Caplan of the New York University Medical Center thinks it will be "the most controversial topic in the next 20 years."

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An article from the Hastings Center, written by scientists associated with the National Institutes of Health, warns that attention must be paid now.

The authors of the report include Greer Donley, a law student at the University of Michigan who interned at NIH; Sara Chandros Hull and Benjamin E. Berkman, on the faculty of NIH. The Hastings Center describes itself as an "independent, nonpartisan, and nonprofit" bioethics research institute.

Currently, prenatal testing is diagnostic, restricted to cases where there is reason to suspect that a child might inherit a disease. Ashkenazi Jews, for instance, are carriers of a rare but terrible childhood disease, Tay-Sachs, and Jewish couples planning to have a family commonly get tested for it. Tests also show if a child will have Down syndrome or cystic fibrosis. Parents then can make a reproductive choice: They can prepare for the child or elect to terminate the pregnancy.

Except for the potential for abortion, current testing is not ethically controversial.

"Prenatal whole genome sequencing differs from current prenatal genetic testing practice in a number of ethically relevant ways," the Hastings report said. "Most notably, whole genome sequencing would radically increase the volume and scope of the available prenatal genetic data."

The report noted that most of that information is currently useless or at best ambiguous. No one knows what 90 percent of genes in a human genome do, and in most cases it takes more than one gene to express themselves for any attribute or disease.

Nonetheless, having that data creates issues. For one thing, the sequencing would likely generate anxiety. Most parents, the report said, think of their unborn child as "normal," but the vast amount of information--most of it they don’t need to know--could change views of what is normal.

The results also could affect parenting. If, for instance, genes associated with intelligence could be located and the parents know the child will not have the genetic variations associated with high IQ, would that affect how they raise the child or their expectations? What if genes for athletic ability were discovered but a fetus lacked favorable versions of those genes? Would parents who want an athletic child be disappointed or even terminate the pregnancy?

Finally, the report said, is the question of privacy. What happens when the privacy of the parents clashes with the privacy of the person yet to be born? What if the genome says the person will suffer a terrible disease later in life? What if they are carriers of genetic disease? Don’t the offspring have a right not to know if they chose?

Parents who act on the information from the test are making decisions for another human that the other human might not make for themselves, Caplan and the Hastings authors agree. Do they have the right?

Genetic tests exist for a number of lethal hereditary diseases that strike later in life, such as Huntington’s disease, and many potential carriers of the genes for Huntington’s have chosen not to know if they have the genes.

The difficulty, Caplan said, is that much of what the tests will show can be misleading. Just because you are genetically susceptible to heart disease doesn’t mean you are going to have heart disease.

"All genetic stuff is probabilistic," Caplan said. "It is beyond argument that we have a difficult time dealing with risk."

Additionally, society has a problem defining what a disease is as opposed to what is simply a difference. People think that if doctors test for it, it must be a disease, he said.

"And anyone who thinks that information that can lead to abortion isn't going to be controversial has been asleep since Roe v. Wade," Caplan said.

So far the controversy is in the future. Pamela Knight, a genetic counselor in Chatham, N.J., said no one has yet come to her with that kind of information and she doesn’t know what she would do if they did. Knight said that making predictions from genetic information is extremely difficult.

"We are nowhere where near predicting those things," Knight said. Additionally, any of the results are not medically actionable--there is nothing medicine can do about them.

"It’s very, very hard to know how to counsel people," Knight said.

The Hastings Center report recommended that the medical community decide which information should be offered to parents, and which not. The report said a child’s’ right to know his or her genetic information should not be breached unless the child would clearly benefit from that knowledge.