In 2003, back when such things remained unpredictable, a woman gave birth to a baby boy with Down syndrome. Her family was shocked. She had undergone the standard screening tests while pregnant—a blood test followed by an ultrasound—but the results had come back negative. Nor did she have the risk factors associated with Down, like advanced maternal age; she was 32. “She was not prepared for this,” recalls Matthew Rabinowitz, her brother. When the boy died six days later, his mother was devastated.
The event left a deep impression on Rabinowitz. A young Silicon Valley entrepreneur who had recently left Stanford with a Ph.D. in electrical engineering, he had just sold the second of two successful IT startups and was casting about for a new venture. Current methods of prenatal screening carry a significant margin of error, and his sister’s false negative suggested an opportunity. “I saw that we were applying our information technology and signal processing to various aspects of life, including cell phones and laptops, but not enough to the area of helping parents have healthy children,” says Rabinowitz.
A scientist in Hong Kong had recently shown that a pregnant woman’s blood contains a small amount of fetal DNA, and the prenatal screening world was buzzing about the potential of that discovery. Accurate blood tests, it was said, might soon reveal abundant information about the fetus as early as seven weeks of pregnancy. Rabinowitz drew on that excitement in 2004 when he founded Gene Security Network, later renamed Natera. Among the tests the company would develop was one to diagnose Down syndrome.
That test, called Parental Support, is currently in trials funded by the National Institutes of Health. Natera is one of several companies vying to commercialize fetal DNA tests, or noninvasive prenatal diagnosis (NIPD). A few years ago, a handful of these companies began offering NIPD to determine fetal sex and detect Rh-factor incompatibility—left undiagnosed, a woman with Rh-negative blood carrying an Rh-positive baby can produce antibodies that attack the baby’s blood cells. Recently, we’ve seen a new wave of NIPD applications: Beginning last fall, the San Diego-based company Sequenom rolled out tests for Down syndrome and Trisomies 13 and 18, and Silicon Valley-based Verinata entered the market with tests for the same conditions in March. Rabinowitz expects Parental Support to be available by the end of the year. (He claims Natera’s technology is more accurate than other tests.)
Now insurance companies are getting involved. Last week, Sequenom announced a partnership with the managed health care company MultiPlan, and others are marketing heavily to insurers. The tests currently available still carry a margin of error and thus can’t yet be sold as a replacement for the likes of amniocentesis. Even as a supplement to existing methods, though, NIPD could be commonly used with high-risk women, predicts an article in the April issue of the insurance industry magazine Managed Care. And as companies like Sequenom and Natera boost their accuracy rates, Managed Care says, NIPD “has potential to become a standard screening procedure.” Because blood tests are less invasive than existing screening methods, and because they help insurers avoid the long-term costs of caring for people with expensive medical conditions and disabilities, they aren’t a hard business sell.
The potential benefits of NIPD are many: elimination of the risks associated with amniocentesis, the replacement of aggravating probabilities with accurate information, and more time for expectant parents to make difficult decisions. But because insurance providers have an incentive to cover them, fetal DNA tests stand to be introduced before we have time to consider the slew of ethical and political challenges they will introduce.
Scientists have known for decades that the blood of a pregnant woman contains a few stray fetal cells. In the 1990s, labs began exploring blood-borne fetal cell testing as an alternative to amniocentesis, which carries a risk of miscarriage. But gleaning information from those cells entails the difficult process of distinguishing them from the mother’s cells—and from fetal cells from earlier pregnancies, which can linger in a woman’s blood long after a baby is born.
Then, in 1997, Dennis Lo, a medical researcher at Chinese University of Hong Kong, discovered that the mother’s blood also contains floating strands of fetal DNA unattached to cells. Today scientists commonly believe the fetus contributes about 10 to15 percent of the DNA in the mother’s plasma. Lo licensed a technique of analyzing cell-free fetal DNA, or cffDNA, to Sequenom in 2005, and the batch of tests the company recently introduced are based on his technology.
Lo says an accurate Down syndrome test was originally considered the Holy Grail of prenatal diagnosis. But in the process of reaching that target, scientists also developed methods of determining fetal sex, which is one of the easier qualities to test for—and which became the first commercialized by companies looking to capitalize on Lo’s discovery. While fetal sexing is helpful for couples with a genetic propensity toward sex-linked diseases like hemophilia, companies like Consumer Genetics, DNA Plus, and Prenatal Genetics Center now offer NIPD direct-to-consumer for parents simply intent on getting a girl or boy. In 2005, an early-generation mail-order blood test, Baby Gender Mentor, briefly inspired a media frenzy culminating in an appearance on the Today show—before it was found to be inaccurate. (Disappointed parents filed a class-action suit, and Acu-Gen Biolab, the company offering the test, filed for bankruptcy.)