Sunday, December 21, 2008

Baylor College of Medicine develops powerful, controversial prenatal DNA test

From the Houston Chronicle:

Baylor College of Medicine is at the forefront of new DNA testing that screens fetuses for hundreds of genetic abnormalities — testing touted for diagnosing previously undetectable disorders but sparking debate because it's sure to result in more abortions.

A Baylor laboratory is offering and promoting the cutting-edge service, also the subject of a large government-funded study. The service exposes fetal cells taken from a pregnant woman's uterus for standard chromosomal testing to more sophisticated analysis.

"This is the beginning of a sea change in prenatal diagnosis," said Dr. Arthur Beaudet, who chairs molecular and human genetics at Baylor and leads the effort. "I think it will replace current prenatal screening within five years, becoming the new test of choice for couples who want maximum information about their developing fetus."

The ethical debate about the testing ranges from whether its accuracy is well-enough established to provide results to anxious parents; to whether it should be regulated by government; to whether such screening reflects a trend toward eugenics, in which society eliminates the defective.

Advocates say the test uncovers tragic conditions, allowing couples to terminate the pregnancy and spare themselves the emotionally and financially exhausting ordeal of caring for a severely disabled child. They say it can ease fears if the testing comes back negative or help parents prepare for a handicapped child if it's positive.

The testing identifies more than 200 genetic syndromes, many quite rare, most involving some form of mental retardation. Many of the conditions are evident at birth, but others do not show up until sometime during the first two years of life.

The screening, also available commercially at Emory University and a private lab in Spokane, Wash., does not target conditions for which there is any treatment in utero or a curative treatment after birth.

As such, it echoes fetal screening for Down Syndrome, the subject of recent controversy after the American College of Obstetricians and Gynecologists' 2007 call for the test to be offered to all pregnant women, not just those 35 or older. Eighty to 95 percent of women who receive a Down Syndrome diagnosis after such screening abort, according to studies cited by the National Down Syndrome Society.

"There are troublesome implications to those statistics and the new testing," says Dr. Mary Mahowald, a University of Chicago ethicist. "They suggest an attitude that deems the lives of people with disabilities not worth living. They're also troublesome because the fewer people with disabilities there are, the more likely they are to be victims of discrimination."

Among those who agree with Mahowald is Bob Kafka, Texas organizer of Not Dead Yet, a disability rights group. He urges Baylor to consult with disability rights activists in Houston to better understand that "this is a civil rights issue for us."

But Baylor's Beaudet argues that the institution is just responding to parents who've said they wish they'd known ahead of time that such a burden was in their future. Children with some of the conditions detected by the screening never walk, talk or eat on their own, he says, and their care can be lifelong.

Baylor has offered the test since late 2005, technology that arose out of its work as a leading research institute on the mammoth federal project mapping the human genome as well as clinical efforts to improve the quality of prenatal diagnosis.

So far, demand for the test has been fairly minimal, says Beaudet, who estimates his lab performs two to four analyses per week. In all, it has conducted about 500 tests.

The charge for the test is $1,600, of which, Beaudet says, insurance usually pays a portion. He says he expects insurance eventually will cover the total amount, as it does now for amniocentesis or chorionic villus sampling, the current standard types of genetic testing for which fetal cells are obtained.

The new test uses a computer chip to analyze those cells for defective bits of the patient's genetic material. Too much or too little of such material can lead to conditions not detected by standard genetic analysis.

"As long as the information is reliable, a pregnant woman has a right to know as much as possible about the kind of parenting she'd face," says William Winslade, a bioethicist at the University of Texas Medical Branch at Galveston. "She may feel that she isn't up to the challenge of caring for a handicapped child or that she doesn't want to increase suffering in the world."

To many observers, the reliability of the information is the fundamental question. They question whether genetics has progressed to the point where much of the data retrieved from the testing can be relied on to be meaningful. They say certain diagnostic information may cause prospective parents undue worry, occasionally resulting in decisions to abort a fetus that might have turned out to be a healthy child.

For that reason, many critics argue that before offering the test commercially, it would be best to complete the ongoing multi-institutional study, now evaluating the technology in 4,000 pregnancies. Emory and Columbia universities as well as Baylor are participating.

But Beaudet downplays the concern. He says the diagnoses are clear-cut in the vast majority of cases. Testing results are ambiguous — say, a 50-50 chance the baby would have a particular disorder — just 1 percent of the time, he says.

Such results turned up three times in 300 cases on which Baylor reported in the Nov. 14 issue of Prenatal Diagnosis. The screening found clear-cut abnormalities in 15 of the cases. Five of the couples receiving such news opted to terminate the pregnancy. None of the couples receiving the "uncertain" diagnosis did.

Beaudet notes that prior to testing, parents are told that the screening may return ambiguous information. They, like all parents using the service, are provided genetic counseling.

"But what kind of counseling?" asks University of Pennsylvania bioethicist Art Caplan. "I think people undergoing this testing need to hear from people who've raised kids with these kinds of issues, or the disabled themselves."

Some critics fear that although institutions like Baylor provide counseling, many private, non-academic labs likely to offer the testing in the future won't. They say the testing cries out for U.S. Food and Drug Administration regulation.

In December 2005, an editorial in the journal Nature called for increased regulation of the testing, saying Baylor's service creates additional urgency. If misdiagnoses occur, the editorial said, "children may be born with unexpected disease or fetuses may be terminated on the basis of false information. Let's hope that such episodes don't have to be documented before the FDA acts."

Beaudet says lab officials met with the FDA in 2006, but nothing came of it, even though the officials said they planned to use the agency's regulatory authority in some way. Beaudet says Baylor told the FDA the lab would do whatever the agency asks.

Chicago bioethicist Mahowald's fear, regardless of whether the FDA gets involved, is that the testing will mostly be utilized by affluent people, having disabled people primarily a phenomenon of the poor.

In any event, in the minds of many ethicists, the testing suggests the arrival of a new eugenics, not state-run but voluntary. They debate whether it's a "good or bad eugenics," noting that before Adolf Hitler gave it a bad name, eugenics was science's hope for a better future, the answer to economic inequities and social ills.

Beaudet acknowledges the testing does reflect "a kind of eugenics." He says it detects conditions that are as or more severe than Down Syndrome, whose impairment of mental function ranges in severity but is usually classified as mild to moderate. Beaudet also notes the conditions found often involve numerous abnormalities.

"Baylor's testing is one of the world's most cutting-edge clinical research programs in an exciting and rapidly changing area of medicine," says Dr. Bruce Patsner, a research professor at the University of Houston's Health Law and Policy Institute and a former FDA official. "The question is, is it ready for prime time?"