Looking for the Telltale Gene

A new genetic test allows parents to peer into their unborn children's medical future. Are we ready for this knowledge? A Columbia study looks for answers.

by Claudia Kalb Published Spring 2013
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Over the next few years, more and more women will face the decision of whether or not to test their unborn children for genetic abnormalities. The new test comes with emotional risks because it will sometimes pick up oddities in a baby’s DNA that are too subtle for geneticists to base any firm conclusions upon, thus leaving parents feeling anxious and helpless.

“Some people are afraid of change, and they are afraid of new information.”
— Ronald Wapner

Ronald Wapner, the director of reproductive genetics at CUMC and vice chairman for research in the department of obstetrics and gynecology, is leading a federally funded study that has provided thousands of women with the powerful new genetic test that was used on Bermudez’s baby. The purpose of his study is to determine if this test generates information that is useful to doctors and parents, and therefore should be offered to all expectant mothers.

“This might mean that a doctor is able to diagnose a genetic disorder in the womb and treat it properly as soon as the child comes into the world,” Wapner says. “Or it could mean helping a mother make a more informed choice about whether or not to continue with her pregnancy.”

A more difficult question, however, is this: will parents be glad they received this information? Or will they regret ever having peeked at their baby’s DNA?

Searching for signs

Prenatal genetic testing emerged in the 1970s, when obstetricians started to recommend amniocentesis for pregnant women over the age of thirty-five. The first common condition that scientists learned to preemptively diagnose was Down syndrome, which stood out because it is caused by the presence of a whole extra chromosome. Soon, they were also spotting the large chromosomal anomalies that cause Tay-Sachs disease, sickle-cell anemia, and several disorders of the neural tube, which is the embryo’s precursor to the brain and spinal cord.

Wapner, a sixty-five-year-old obstetrician who came to Columbia from Drexel University in 2005, has been trying to improve prenatal diagnosis his entire career. In the early 1980s, he was instrumental in developing chorionic villus sampling (CVS), a procedure in which fetal cells are extracted from a woman’s placenta rather than from her amniotic fluid. CVS can be done at an earlier stage of pregnancy — in the first trimester, versus the second — and is now a popular alternative to amniocentesis, although some women still get amniocentesis because it is easier for physicians to administer and is more widely available.

Ronald Wapner / Photograph Jörg MeyerWapner’s most important contribution, though, may turn out to be his advancement of microarray analysis, the genetic test that Bermudez underwent last summer. The idea is simple: rather than limiting oneself to what can be spotted visually, why not use computers to identify the minutest discrepancies in a baby’s DNA? The technology is not new. By the time Wapner proposed examining fetal tissue this way in 2006, physicians had been analyzing the DNA of sick children by microarray for a few years. The technique was especially useful in spotting rare disorders that pediatricians had trouble diagnosing any other way.

“Say you have a youngster with a seemingly random combination of learning difficulties and physical problems, like a heart defect and cleft palate,” says Wapner. “If you do the microarray, you may discover he has a small piece of chromosome 22 missing. That indicates it’s DiGeorge syndrome. And it means he’s got a 25 percent chance of developing schizophrenia. So now you can be on the lookout for that, too.”

With such a sophisticated tool, however, came thorny ethical questions. Obstetricians knew from experience that many pregnant women who opt for genetic testing are those who, after having received a troubling result on an ultrasound, are considering abortion. The method of analysis using microscopes, which is called karyotyping, was generally considered a useful tool for helping them to make this decision because it identified large, clearly defined genetic defects. The microarray test, on the other hand, would detect not only the genetic signatures of rare diseases like DiGeorge syndrome but also many other DNA flaws whose impact on the body were not yet fully understood. This raised the possibility that babies could be aborted for having slight, potentially harmless DNA irregularities.

At the same time that Wapner and several other scientists were developing a prenatal version of the test, however, rapid progress was being made in linking subtle DNA mistakes with specific conditions. These advances emboldened Wapner — a tall, wild-haired native of Wilmington, Delaware — and a few of his influential colleagues, including Baylor University’s Art Beaudet, Emory University’s David Ledbetter, and Washington State University’s Lisa Schaffer, to articulate a new vision for prenatal genetic testing, one driven not merely by the desire to help women decide whether or not to abort high-risk pregnancies but also by the hope of diagnosing and treating a number of disorders as early in life as possible.

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