Sun, Mar. 03, 2002
By Faye Flam
Knight Ridder Newspapers
Mother sets off flurry of debate for use of tests to avoid passing on early-onset Alzheimer's
Is it ethical to use high-tech genetic selection to ensure that a child is born without an unwanted hereditary trait?
That question is roiling the medical world after last week's announcement that a 30-year-old woman used genetic screening to avoid passing on a form of early-onset Alzheimer's disease to her baby daughter.
It was the first use of such genetic testing to prevent that disease, and it raised questions about when, or if, science should intervene in a person's genetic makeup.
"There are some enormous ethical issues -- much bigger than with cloning," said Arthur Caplan, a medical ethicist at the University of Pennsylvania.
While scientists continue to discover genes associated with traits or diseases, society has yet to decide when genetic screening is appropriate, Caplan said. Which traits are considered serious enough? "It gets to what we consider a disease," he said.
Cases such as the early-onset Alzheimer's gene, he said, show a clear benefit because the disease is tragic and deadly.
But soon, people may be able to do such screening for juvenile diabetes, or a predisposition to autism, schizophrenia, asthma or multiple sclerosis.
And from there, they might be able to screen out other traits, such as short stature, or a propensity for plumpness or a tendency to suffer depression or to go bald.
"We need to have a long debate about when we'll impose our tastes, preferences and biases," Caplan said.
The woman in this case carries a gene that makes it almost inevitable that she will die of Alzheimer's disease by her mid-30s or early 40s. Her father had died of the disease at 42, and a sister at 38. A brother became demented with it at 35.
At 30, the woman had been tested and knew she carried the gene, and therefore had a 50-50 chance of passing it to a child. But with in-vitro fertilization, she was able to avoid those odds.
Her doctor, Yury Verlinsky of the Reproductive Genetics Institute in Chicago, retrieved 23 eggs from her ovaries and used genetic tests to select four that did not carry the gene. These were fertilized with her husband's sperm in a laboratory and implanted in her uterus, the same way that doctors use in-vitro fertilization to help infertile women become pregnant.
The birth of the baby about 17 months ago was announced last week in the Journal of the American Medical Association.
The mother's gene for early-onset Alzheimer's is extremely rare: Only 20 to 30 families are known to carry the genetic abnormality, said its discoverer, Rudy Tanzi of Massachusetts General Hospital.
Scientists have also identified a gene, called APOE, that everyone carries in one of four varieties. But one of those four, labeled APOE-4, gives people a higher probability of contracting Alzheimer's disease in old age. But it's only a probability, Tanzi said; many people with APOE-4 live to old age with no signs of Alzheimer's.
Screening for this, he said, seems much less justified than for the early-onset gene.
Verlinsky, the mother's doctor who did the screening procedure, said preimplantation diagnosis has been used to screen for more than 100 diseases, including cystic fibrosis, hemophilia, Tay-Sachs disease, and Huntington's disease. Verlinsky estimates that 1,000 babies worldwide have been born after genetic selection.
Rather than preimplantation diagnosis, parents concerned about genetic diseases can choose to get pregnant and have the fetus tested and then aborted if it carries a genetic disease. In the case of this Alzheimer's gene, there would be a 50 percent risk.
This in-vitro technique, which costs more than $1,000, avoids the abortion decision.
The Journal of the American Medical Association published an accompanying commentary written jointly by a bioethicist and a genetics expert who questioned the woman's decision to have children at all, given that she would soon be unable to take care of them, and they would have to suffer through her deterioration and death.
Verlinsky said this was a personal ethical issue to be decided by the woman and her family.
"We can't promise any child that they will always have two parents to care for them," said Christina Masciangelo, a genetic counselor at Verlinsky's Chicago clinic. "Accidents happen, sicknesses occur, people get divorced."
Dr. Margaret Pericak-Vance, director of the Center for Human Genetics at Duke University, said: "Who's going to judge who will be a good parent or not?"
"The ultimate decision should rest with the individual, as long as it's an educated decision. I'm not saying everybody will make the right choices. But you get into a dangerous zone when you make decisions about who can or cannot reproduce."
While Pericak-Vance did not question the woman's right to have children, she did have ethical concerns about using genetic tests to weed out embryos carrying a gene that might do no harm for 40 years. Currently, most preimplantation diagnosis -- and most pregnancy termination after amniocentesis -- is done to prevent diseases that would cause severe illness or death in childhood, not decades later.
But as more genes are identified for late-onset diseases, the question will come up again and again. And many people who would not have an abortion for a late-onset condition would find embryo selection acceptable.
"Who judges what's quality of life?" Pericak-Vance asked. "If somebody lives 30 years, 40 productive years, is that something that shouldn't happen?"
For Pericak-Vance, it is a deeply personal question. "I had a 14-year-old son who died suddenly," she said. He had a medical condition, unknown to his parents, that caused blood clots in the brain.
"Knowing he was going to die, would I have said, `No, I don't want him?' Never. For those 14 years, he was the most wonderful son you could have."
But, Pericak-Vance added, "Somebody else might say no, the loss is too great to bear."
Dr. William Thies, vice president of medical and scientific affairs for the Alzheimer's Association, said: "What's clear is that as new pieces of technology become available, there's a debate that's not really a scientific debate. It needs to be out in the broader community about what's acceptable and what's not. The community says genetic testing that leads to family planning is OK in some cases. But for a disease 30 years out, does that change? You need lots of people involved in this debate before you come to a conclusion about what society wants to happen."
Penn ethicist Caplan said his concern is that genetic screening could become almost obligatory as more disease-associated genes are found and the technology becomes easier to use and cheaper.
Cloning, he said, has attracted all the attention, but he predicts little demand for cloning, "unless you're really, really vain."
"But being able to pick traits in people -- to avoid disease and create healthier children," that's what people will want, he said.
Hundreds of genetic diseases exist, but there are no standards for when a test should be offered or how accurate such a test needs to be, Caplan said.
Some ethicists worry about the way this technology will change ordinary parenting.
"It ends up putting enormous responsibility on each pregnant woman to justify the quality of each child she's giving birth to," said Barbara Katz Rothman, a sociologist at the City University of New York.
"It's kind of scary," she said, noting that we all carry various genetic differences that could be seen as liabilities. With enough testing, she said, we might find that "nobody's good enough."
The New York Times contributed to this report