Ferreting out flawed embryos
By Lisa M. Krieger
Mercury News
Posted on Tue, Mar. 12, 2002
``Survival of the fittest'' is moving from the wilderness to the laboratory, where parents can pick and choose their future children based on information contained in a tiny embryo's genetic code.
Doctors in the Bay Area have used this genetic test, called preimplantation genetic diagnosis, or PGD, to identify human embryos that lack deadly mutations, allowing more than a dozen local families to have children free of illnesses that have long haunted their families.
By preventing the birth of babies with disabilities and disease, PGD offers hope to would-be parents who carry severe genetic defects. Embryos with defects are discarded or donated to research; healthy embryos are implanted.
``These are people who would be faced with a very serious burden if their child was born with a lethal or life-altering disease,'' said Dr. David Adamson of San Jose, who has delivered healthy babies to two South Bay couples with a family history of severe genetic illness.
The test is expensive, and its use is limited to only certain genetic disorders. But it poses the possibility that, someday, parents may choose to eliminate not only lethal diseases, such as cystic fibrosis or Huntington's disease, but also less life-threatening traits, such as manic depression, morbid obesity or a predisposition to cancer.
Critics, fearing an erosion of human diversity and an era of ``designer babies,'' ask whether it is ethical to cull embryos predisposed to diseases that may never happen -- or could be curable, by the time they appear in 40 or 50 years.
At a crossroads
The technique stands at the crossroads of new developments in the fields of fertility and genetics. Embryos are created using in vitro fertilization, then tested using DNA analysis when they are only 3 days old and only a few cells in size. While genetic disease has long been detectable using other prenatal tests, such as amniocentesis or chorionic villus sampling, the consequences are more emotionally wrenching because, unlike PGD, the embryo is already nestled in the womb and far more mature.
One South Bay couple used PGD to screen out embryos with a double dose of the gene for sickle cell anemia, an untreatable and painful blood disease than ran in their families, said Adamson, their doctor. Another couple he treated used the test to identify embryos that carried the gene for Huntington's disease, a devastating neurological disease that killed a grandmother.
Such choices are welcomed by many families hoping for a way to escape generations of crippling illness.
``I would have used this test in a second,'' said Robert Bishop of north Salt Lake City, father of five children. His former wife, Amy -- the children's mother -- is institutionalized with Huntington's disease, a deadly inherited neurological disorder. ``You don't want to play Russian roulette with your children.''
Because few dispute the wisdom of sparing a newborn a certain death, the testing has been almost universally accepted in the medical community. In the Bay Area, fertility clinics in San Jose, Palo Alto, San Francisco and Berkeley offer so-called ``embryo biopsies,'' in which a single cell is extracted for testing, not harming the embryo. The cell is then quickly shipped to one of the handful of specialized labs that do DNA diagnostic testing.
``As the ease of testing increases, so does the perception that it is a logical extension of good prenatal care,'' according to a recent report by Eric Parens, associate for philosophical studies at the bioethics think tank the Hastings Center of Garrison, N.Y.; and Adrienne Ash, professor of biology, ethics and politics of human reproduction at Wellesley College in Massachusetts.
``Today, we test for one trait at a time. In the future, however, with advances in bio-chip technology, it will be possible to test simultaneously for as many traits as one would like,'' wrote Parens and Ash. They worry that prospective parents who get prenatal genetic information do not get enough information about living with a disability.
Advances in testing
The number and variety of conditions for which tests are available grows almost daily. It is now possible to test for gene mutations associated with more than 400 conditions, ranging from the deadly Tay-Sachs disease to the minor condition called polydactyly, or the growth of an extra little finger.
``I believe in the future that sex and reproduction will be two separate acts,'' said Dr. Barry Behr, director of in vitro fertility and assisted reproduction at Stanford University Medical Center.
``We have not scratched the surface of the potential of these techniques. Diseases will be prevented,'' Behr said. ``In theory, any disease that is hereditary, we can test for.''
Increasingly, PGD seeks genes for a range of illnesses that do not kill at birth but develop far later in life -- raising the possibility that someone who could have made important contributions to society instead perishes in the lab. Perhaps the afflicted embryos would have enjoyed a richly rewarding life for years, even decades, prior to the onset of disease. Or maybe they would be saved by a cure to be developed in their lifetime.
The test stirred debate last month with the news that doctors at Chicago's Reproductive Genetics Institute delivered a healthy baby girl to a woman who carries the gene for rare early-onset Alzheimer's disease -- which robs the mind in one's 30s and 40s.
The mother, while healthy, has a brother and sister who developed Alzheimer's in midlife. Tests show that she, too, carries the mutation called V717L, linked to the formation of the brain-clogging protein deposits that identify Alzheimer's. She is now attempting a second pregnancy.
The lab also helped conceive a baby boy born to a New York couple plagued by Li-Fraumeni syndrome, an inherited predisposition to many forms of cancer caused by a defect in a tumor-suppressing gene called p53. The father was first diagnosed with cancer at age 2, then again at age 31. Only seven of the couple's 18 embryos had normal p53 genes; of these, one was implanted in the wife's womb and delivered to term. The baby's birth was announced in June.
Also controversial was the birth in Denver last year of Adam Nash, whose embryo had been selected from among 15 others because it was a bone marrow match for his older sister, afflicted with lethal anemia. Cells transplanted from Adam's umbilical cord saved his sister's life.
Breaking a chain
Some families whose genes may prompt disease say the test can break a generations-long chain of ancestral illness. The family of Amy Bishop had been told that her paternal grandmother had been taken from her home in a straitjacket and institutionalized as a chronic alcoholic -- a tale that suggests to the family that she suffered from Huntington's disease. Amy's father, also afflicted, unknowingly passed on the gene for Huntington's disease to Amy and her younger brother and sister. The five children of Amy and Robert Bishop have not been tested for the gene.
``The disease is not just a killer of individuals. It destroys families. There's no way out,'' said Robert Bishop, a software developer whose family lost their health insurance and faced bankruptcy after his wife spent 168 days in the lock-down unit of a hospital psychiatric ward -- at a cost of $1,500 day.
``My 17-year-old daughter has said, `Dad, who will ever marry me? How will I ever have children?' '' Bishop said. ``It is a terrible death. The brain dies slowly, gradually taking away everything you are.''
Those with less debilitating illnesses and disabilities worry that indiscriminate use of the test will create a population of what society considers ``normal'' and ``healthy.'' Future generations may have far fewer dwarfs, for instance. They note that people who have endured disability and illness are different -- they have unique experiences that the larger society can benefit from. Culling these embryos from the gene pool suggests that people with disabilities and illnesses should never have been born, they said.
Ethics concerns
Catholic ethicists share the concern over this new development in reproductive technology. At a recent symposium at the University of Illinois-Chicago, William May of the John Paul Institute for Studies on Marriage and Family said that an embryo with defective genes ``is not a potential person. It is a person with potential, an identifiable member of the human species.'' According to University of Chicago ethicist Jean Bethke Elshtain, embryo testing could ``narrow our definition of humanity'' and implies that those suffering from disabilities should never be born.
Worse, the $15,000 to $20,000 cost of IVF and PGD is not covered by insurance, and thus is available only for those who can afford it. Most couples either pay for the procedure themselves, or give up on the idea of conceiving children or decide to throw the genetic dice.
There is also the sticky problem of hundreds of unused embryos, healthy but not implanted, stored in a frozen twilight zone of potential life. Critics charge that there is little regulation of the field and no standards or accepted ``error rates'' for these tests. The industry is being internally governed by an informal network of physicians and clinics.
Moreover, the vast majority of birth defects are caused by something other than an inherited genetic error. For instance, pre-embryo testing cannot detect the spinal-cord defect called spina bifida, which occurs later in pregnancy when the bones and skin fail to close around the spine's nerves.
``It's a very individual choice whether to use the test'' on prospective children, said Amy Russell of New York City, who suffers from moderate to severe depression, a disease that in some individuals seems to have genetic origins. Because of her struggle with depression, ``In some ways, I'm a richer person for it . . . but I wouldn't wish it on anyone.''
Barbara Brenner, a breast cancer survivor who founded Breast Cancer Action in San Francisco, believes that medical focus should instead be placed on disease prevention and treatment. ``If we start screening for every single genetic mutation related to cancer, we're paddling up a very dangerous creek,'' she said.
Breast cancer has become a prime example of the potential -- and shortfalls -- of genetic testing. Three genes -- BRCA1, BRCA2 and BRCA3 -- have been linked to risk for some forms of breast cancer. But others may not be genetically based, and even test results showing risky genes are no guarantee a woman will get breast cancer.
``There are 400 different mutations on the BRCA1 gene alone. Is one associated with high risk? Low risk? We don't know,'' Brenner said. ``We'd better be cautious and thoughtful about where we're going with this. The science is getting way out ahead of public policy.''
Medicine is pushing us into making decisions we never thought of, doctors agree.
``We shouldn't exploit this powerful technology for trivial reasons,'' said Stanford's Behr. ``Someone may misuse it. There will always be mavericks. But this shouldn't cloud its future. There are huge benefits.
``In the future, when you use IVF to have a baby, you can ensure that it won't develop diabetes or cancer when they age.
``Wouldn't you do that?''
Contact Lisa Krieger at lkrieger@sjmercury.com or (408) 920-5565. |
