A handful of biotech companies are racing to market a new generation of tests for Down syndrome, a development that promises a safer way to spot the most common genetic cause of mental retardation early in pregnancy even as it weaves a thicket of moral, medical, political and regulatory concerns.
Doctors recommend that all pregnant women be offered screening for Down syndrome, and about half of women undergo the tests. But the current tests often produce confusing, ambiguous results, unnecessarily alarming couples or falsely reassuring them. The new tests are designed to offer more definitive results early in the pregnancy.
But with the first new approach due to become available this spring, the tests are renewing questions about why regulators do not require such innovations to be proved reliable before being offered to the public.
Abortion opponents, meanwhile, fear that the technology may prompt more couples to terminate pregnancies. And advocates for the disabled, noting that couples are often poorly informed about the syndrome, worry that more of them may feel pressured to abort. They also fear a dwindling number of those born with the condition, along with the prospect of increased discrimination against them and their families.
"We have a history in this country of a eugenics movement where people tried to eliminate certain people from the gene pool," said Andrew J. Imparato of the American Association of People With Disabilities. "People could start wondering, 'How did you get born?' "
'Just the first wave in a salvo of new tests'
The quandaries being raised by the tests illustrate the morass of issues that will arise as scientific and technological advances produce more tests to identify markers for genetic conditions -- before conception, during pregnancy and even after birth.
"This is just the first wave of a salvo of new tests," said W. Gregory Feero of the National Human Genome Research Institute. "We are at a time where you will be able to test for many things and will be left with many serious questions -- both scientific and moral -- about how to interpret and what to do with the information."
The new tests for Down syndrome come as advocates pressure Congress to fund a law passed last year aimed at ensuring that couples get accurate information about genetic conditions and at providing support for women who decide to keep their affected children or put them up for adoption.
"These tests make this all the more important," said Madeleine Will of the National Down Syndrome Society, which is seeking $25 million over five years to implement the legislation. Society members are gathering in Washington this week to lobby on this and related issues.
In 2007, the American College of Obstetricians and Gynecologists recommended that all women be offered screening tests for Down syndrome, which causes mental retardation and other health problems. The current tests consist of a combination of blood tests and ultrasounds. Depending on the results, the women may then undergo either amniocentesis or chorionic villus sampling (CVS) to confirm or rule out the diagnosis.
But the screening tests often produce imprecise results, and amniocentesis, the most common definitive test, can cause miscarriages and is not usually performed until the second trimester, when the termination of a pregnancy is much more traumatic and difficult to obtain.
'The Holy Grail of genetic testing'
The new tests take advantage of techniques that can isolate and analyze tiny bits of genetic information from the fetus that circulate in a woman's bloodstream, in this case from cells or free-floating snippets of DNA or the related molecule RNA.
At least four companies are developing such tests, including Sequenom of San Diego, which plans to be the first on the market in June. The other companies hope to have their versions on the market within a year.
"For 50 years, folks have been working to develop a noninvasive genetic test for Down syndrome," said Sequenom chief executive Harry Stylii. "People have described it as the Holy Grail of genetic testing. We are on the cusp of delivering that."
At a meeting of the Society for Maternal-Fetal Medicine in San Diego last month, the company reported that results from 858 women showed that its test did not miss a single case of Down syndrome and produced only one false alarm, making it much more accurate than the currently available screening tests and on a par with amniocentesis.
Initially, Sequenom plans to offer the test as an alternative to the first-trimester screening blood-and-ultrasound test. By reducing false alarms, the test could help many women obtain a more definitive diagnosis without the risks of amniocentesis or chorionic villus sampling.
The company hopes the test will eventually replace amniocentesis and CVS, giving women a safer, definitive diagnosis in the first trimester.
"It will probably take a year or two for doctors to become comfortable with that, but I think that's where we're headed," Stylii said, adding that the technology will probably be used to screen for other genetic disorders as well.
Several experts agreed that the Sequenom test and others in development show great promise, potentially offering women either an earlier chance to end a pregnancy or more time to prepare for caring for a child with disabilities.
"These tests are extraordinarily promising," said Joe Leigh Simpson, president of the American College of Medical Genetics.
But several experts said more extensive studies should be done before the tests are made available.
"There have been many tests in the past that looked promising but ended up not performing as well," said James D. Goldberg, a San Francisco obstetrician who acts as a spokesman for the American College of Obstetricians and Gynecologists. "It's just too early to know whether these numbers are going to hold up."
Lack of regulation
Several experts said those issues illustrate the void left by the Food and Drug Administration's long-standing policy not to regulate such tests.
"Genetic testing and other kinds of tests are increasingly going to be used for making vital treatment decisions. We want to be sure the test results are accurate," said Kathy Hudson of the Genetics and Public Policy Center at Johns Hopkins University.
FDA officials would not comment about specific tests, but a spokesman said the agency has "exercised its regulatory discretion" not to regulate them because they are developed and used by a single laboratory.
Stylii said Sequenom hopes to publish its test data soon, while also sponsoring two large studies involving thousands of women to further validate the test's effectiveness. "We're being very cautious," he said. "We're trying to serve a real need."
Advocates worry that such tests could increase the number of women getting inaccurate information that makes life for people with Down syndrome and their families sound worse than it really is.
"We have a nation of physicians who are unprepared for explaining a diagnosis of Down syndrome," said Brian Skotko, a physician at Children's Hospital in Boston who works with the National Down Syndrome Society. "Many overemphasize the negative consequences or outright urge women to terminate their pregnancies."
Skotko, whose sister has Down syndrome, predicted such tests would result in fewer babies being born with the condition.
"Every day my sister teaches me lots of life lessons -- to laugh when others are mocking me, to keep on trying when obstacles are thrown my way," he said. "If there were a world with fewer people with Down syndrome, I think the world would miss all these important lessons."
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