Genetic screening draws fire from ethicists
IVF pre-implantation diagnosis under question
Should prenatal genetic diagnosis (PGD) be used to screen human embryos for genetic predispositions to certain diseases, not just as a tool to detect genetic markers that definitely indicate the presence of a medical condition?
That’s the challenging question raised a recent report in the Feb. 27, 2002, issue of the Journal of the American Medical Association (JAMA).1
In the report, Verlinsky and colleagues at the Reproductive Genetics Institute of Chicago detail the case of a 30-year-old woman with a genetic marker linked to the development of early-onset Alzheimer’s disease (AD). Although currently asymptomatic, the woman’s sister, brother, and father all have the illness, and genetic testing has shown that she has the same mutation.
In what is thought to be a medical first, the woman underwent two cycles of an in vitro fertilization (IVF) procedure, with all embryos screened for the genetic mutation prior to implantation in her uterus. As a result, the woman gave birth to a baby girl without the mutation and has used the screened IVF procedure to become pregnant a second time.
Using IVF for this procedure (a technique termed pre-implantation genetic diagnosis) instead of traditional PGD, which is ordinarily performed after a woman is already pregnant, allows patients and clinicians to avoid the ethically questionable practice of selectively aborting fetuses affected by mutations that only indicate a strong predisposition to develop a serious disease later in life.
"Pre-implantation genetic diagnosis has been applied to at least 50 different genetic conditions in more than 3,000 clinical cycles," the researchers wrote. "In addition to traditional indications similar to those in prenatal diagnosis, pre-implantation diagnosis was performed for an increasing number of new indications, such as late-onset disorders with genetic predisposition. These conditions have not been an indication for prenatal diagnosis because of potential pregnancy termination, which is highly controversial if performed for genetic predisposition alone."
And, as the researchers acknowledge, the procedure they performed is not without ethical question. "Because the disease never presents at birth or early childhood — and even later — may not be expressed in 100% of cases, the application of pre-implantation genetic diagnosis for AD is still controversial," they wrote. "However, because there is currently no treatment for AD, which may arise despite pre-symptomatic diagnosis and follow-up, pre-implantation genetic diagnosis seems to be the only relief for at-risk couples."
Will society draw the line?
But many ethicists question whether our society will be willing to draw the line between "relief" for parents facing the strong likelihood of a devastating medical condition and eugenics, allowing couples to "design" the baby of their dreams.
"One of the notions we were calling into question is how far ought norms — or the closely held beliefs of a majority — determine what is ethically acceptable," says Roberta Springer-Loewy, PhD, assistant clinical professor in the bioethics program at the University of California-Davis. Loewy and a colleague, Dena Towner, MD, co-wrote a commentary on the procedure in the JAMA issue featuring the report. "I think some of the important questions here ought to include, Should reproductive freedom be considered an absolute right when acting on that right can be shown to result in an undue burden on others?’"
How far do physicians’ responsibility extend?
The study’s participant is thought to be at very high risk for developing symptoms of AD before she reaches her 40s, Towner and Springer-Loewy point out. Therefore, it is very likely that she will not be able to continue to care for these children while they are still at a very young age.
The woman’s sister, they note, had to be placed in an assisted living facility by the time she was in her 40s, and one of the first manifestations of the illness noted in her case was difficulty caring for her two children.
"A child living under these circumstances would be burdened by the mother’s progressive and eventually profound debilitation and eventual premature demise," they wrote. "Of note, if this same child were orphaned, current adoption regulations would prevent this same childless couple from adopting."
While this attitude may seem harsh, they are only trying to point out that medical providers — in fulfilling their duty to patients — should ask the patient to consider all of the available options and alternatives and to consider the different consequences of each option, Springer-Loewy explains.
The parents should consider, for example, the impact that the choices they make will have on the children they conceive, she says. The clinicians themselves should be willing to examine how these choices will affect the larger society. Will these reproductive technologies, amazing as they are, be available only to those who are able to pay? Or will they be available to everyone? If so, what affect would that have?
"To suggest that, by not making assisted reproductive technology [ART] available, physicians or geneticists are accomplices in placing a child at greater risk wrongly implies that there are only two options: pregnancy with ART or pregnancy with no ART. Frankly, there is another responsible option: not to get pregnant. If that sounds harsh, it does so only because so many members of our society have been conditioned to expect to have their desires met, often at the expense of many others not so fortunate," says Springer-Loewy.
While the average person might see nothing wrong with "screening out" embryos with genetic markers for deadly diseases, who defines what diseases are serious enough to be screened for is a difficult question to answer.
"The rub comes in defining what ought to be included under the rubric disease,’" Springer-Loewy states.
"Quick example: In the past century, masturbation has been, at various times, considered a disease (it once had a recommended surgical cure), a sin, and then a normal part of sexuality. We tend to forget that while concepts like disease’ and pathology’ have a purely biological component, they are also social constructs. Deadly diseases — those associated with significant morbidity and mortality and much pain and suffering — that can clearly be delineated certainly ought to be prevented when possible, but the benefits and burdens of such prevention should be distributed equally."
A false distinction?
To simply question the ethics of allowing this type of prenatal screening is in some ways a false distinction, says Adrienne Asch, PhD, the Henry R. Luce Professor in Biology, Ethics, and the Politics of Human Reproduction at Wellesley (MA) College.
"If people question screening for this, then I would ask them, Why they would screen at all?’" Asch states. "What is the difference? The act is selecting. You are selecting out certain embryos based on specific characteristics. Whether you do it at the embryonic stage or the fetal stage, that is what you are doing."
It is not up to the medical providers to be the "gatekeepers" of such technology, but our society as a whole needs to examine the possible consequences and decide whether we want to allow screening for genetic characteristics prior to birth or conception, she says.
"If society wants to screen, then, unfortunately, I think we will soon come to the level of screening for every characteristic you can imagine — musicality, tone deafness, color blindness — because somebody will care," she says.
Reproductive care providers already routinely offer prenatal screening for diseases that are not fatal, she says. What is the true difference between selecting out an embryo that will be affected by a given illness, that has a strong predisposition to an illness or disease, and selecting out for an embryo that will produce a tall child or strong child?
"Physicians are trained to provide medical information — some of which is frequently out of date," she adds. "They are not trained very well in discussing different impairments and disabilities and what life is like living with them."
Providers can refuse to screen for certain conditions because of conscience, if they want to do so, Asch says. But, if they do, they should ask themselves the reason that they screen for anything, she says. "What is wrong with life with Down’s syndrome? What is wrong with life with spina bifida?"
Some ethicists, however, say that concerns about the possible uses and abuses of PGD are overblown. That it will take more time to determine whether the potential even exists for parents to screen for blue eyes and blond hair.
The case covered in the JAMA report detailed a very rare genetic condition — one thought to affect only about a dozen families worldwide, and the chance that the woman will develop the disease are thought to be close to 100%, notes Andrea Bonnicksen, PhD, professor and chair of the political science department at Northern Illinois University and a member of the ethics committee of the American Society of Reproductive Medicine (ASRM).
"This seems to me to be a pretty straightforward case, because it looks like such a rare and deadly disease," she says. Since the development of its 1994 ethical guidelines, ASRM has supported the use of PGD to prevent the birth of children with serious genetic disorders, and this would seem to fall within that parameter.
There is something to be said for letting the technology evolve a little more to see where it will head before deciding where the lines should be drawn, she adds. "It is so difficult to anticipate what the new uses will be. The more experience there is with PGD, the more one is able to anticipate the different conditions under which this should be permissible and we will be able to draw the lines more meaningfully."
1. Verlinsky Y, Rechitsky S, Verlinsky O, et al. Pre-implantation diagnosis for early-onset Alzheimer’s disease caused by V717L mutation. JAMA 2002; 287:1,018-1,021.
- Adrienne Asch, PhD, Wellesley College, 106 Central St., Wellesley, MA 02181.
- Andrea Bonnicksen, PhD, Department of Political Science, Northern Illinois University, DeKalb, IL 60115.
- Roberta Springer-Loewy, PhD, Associate Clinical Professor, Health Care Ethics, University of California, Davis, UCDMC — PSSB 2400, 4150 V St., Sacramento, CA 95817.