MAY 1986, VOL. 43, NO 5 AORN JOURNAL

Ethics

Genetic screening; medical progress prompts ethical questions

enetic screening can be defined as the G systematic search in a population for individuals of a given genetic constitution. Its missions are no different from those of medicine- diagnosis, treatment, and prevention of disease.

Genetic diseases in the United States cause the following:

0 80% of genetic defects, 0 40% of spontaneous abortions,

80% of mental retardation (3% of US population),

0 33% of patients in pediatric wards, and 0 25% of all chronic diseases. Considering the devastating impact of genetic

disease on fetal wastage and human health, screening can be a significant adjunct of preventive medicine. To some, however, it is an evil that has the potential to threaten society by invading privacy and destroying one’s freedom of choice in childbearing. Screening may also stigmatize and emotionally traumatize unaffected individuals who are told they are “carriers” of potentially harmful genes. Both concerns have validity if screening is improperly done.

The most common purpose of genetic screening is to identlfy those persons who are at risk for themselves or their offspring of getting a genetic disease. A recent and perhaps more controversial purpose is the identification of individuals who have genetically determined susceptibilities to environmental agents.

There are two classes of genetic screening. 0

0

Presymptomatic screening-detecting indi- viduals whose own health is threatened. Carrier identification-detecting those

healthy individuals whose genes threaten the health of their future offspring.

Presymptomatic Screening

commonly used form of presymptomatic A genetic screening is newborn screening, which focuses on the early diagnosis of inborn metabolic defects and hypothyroidism. The screening includes all newborn babies without considering family histories. Because the diseases being screened for are recessively inherited, the family history is usually negative. Parents of affected infants are by definition carriers.

Presymptomatic screening needs to be econom- ical, logistically possible, and reliable for diagnosis of disease early enough for treatment. It is important that the diseases are amenable to presymptomatic therapy. For example, neonatal screening for phenylketonuria, which is being done routinely throughout the United States and in other developed countries, has been enormously successful. Problems with phenylketonuria screening involve assuring adequate counseling and treatment if the newborn is affected, informing parents about the tests antenatally, and whether to make the tests mandatory. Parents who have an affected newborn after refusing screening could be considered guilty of child abuse.

A more controversial form of presymptomatic population screening is the screening of employees by industry to identify those with a genetic susceptibility to environmental hazards. For example, individuals found to be mutants for alpha-I-antitrypsin, whose health could be affected

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The effectiveness of screening for a few recessively inherited diseases has been vastly

increased by intrauterine diagnosis.

by pollutants in the workplace, may find their jobs at risk or their health insurance affected by public disclosure. Labor unions believe the screening is an attempt by industry to circumvent its duty to clean up the workplace environment. On the other hand, knowledge of specific genetic susceptibilities to such diseases as pulmonary emphysema, lung cancer, and heart disease may significantly affect a person’s lifestyle and choice of occupation and can be an important form of preventive medicine.

Carrier Identifiation

major new area in clinical genetics has been A detecting those healthy carriers whose genes could threaten the health of future offspring. This carrier identification can be done by screening specific subpopulations in which carriers of a particular harmful mutant gene are common. For example, many Jews of Eastern European origin carry the gene for Tay-Sachs disease, and roughly 10% of blacks are carriers of the sickle cell anemia gene.

Those diseases, for which there are no effective treatments, are characterized by recessive inheritance; hence, both parents of an affected person are carriers. When both parents are carriers for the same gene (heterozygotes), there is a 25% chance with each conception of having an affected child (homozygote). The effectiveness of screening for a few recessively inherited diseases has been vastly increased by intrauterine diagnosis. The significantly lowered number of newborns in the United States affected by Tay-Sachs disease is an example of how effective intrauterine diagnosis can be when both parents are carriers.

When both members of a couple have been identified as Tay-Sachs carriers, they have several options to prevent having an affected child. They can get pregnant and selectively abort affected fetuses; get pregnant by artificial insemination with

sperm from a noncarrier donor; or adopt a child and not reproduce. Of course, a carrier can choose a noncarrier mate.

Those three options are the main choices when the carrier can be identified. For many other diseases (eg, cystic fibrosis), preventing conception is the main choice because carriers can only be identified by virtue of the fact they have an affected child. However, progress is being made and we may soon be able to diagnose cystic fibrosis by amniocentesis.

Major problems with recessive-inheritance screening have been getting informed consent and explaining the significance of being a carrier to those at risk. Geneticists must take care not to affect the self-image of carriers. For example, in some communities in Greece, the carrier is stigmatized and, as a result, has trouble finding a mate. In one sense, identified carriers are fortunate because tests can detect the presence of the same mutant gene in them and their mates. Such testing is not available for many recessively inherited diseases.

The carriers’ privacy must be respected because knowledge of carrier status may affect their job status and insurability despite the fact that carriers are unaffected by the mutant gene. However, in a population in which the mutant gene is common, the disease serious, and the testing accurate and inexpensive, screening can be effective. Careful advanced planning, education, and follow-up for carriers and noncarriers are required. On the positive side, the testing permits couples, both of whom are carriers for the same harmful gene, to make informed choices regarding reproduction.

Family Screening

amily screening is the most common type of F genetic screening. It is used by people who wish to know their chances or that of future offspring of having a specilic disease. Frequently

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the pedigree analysis will identify others in the family who are ignorant of their potential risk. One ethical dilemma concerns offering family members that unsolicited information. Undoubt- edly, some would rather not know. The situation becomes particularly tricky if the person being consulted does not want relatives to know about his/her risks. How much should confidentiality be respected when relatives or their future offspring are at significant risk of serious or fatal disease?

Huntington’s chorea poses a particular dilemma. This tragic neurodegenerative condition often does not become evident before a person is 35 years old and may already have children. Because the disease is dominantly inherited, any offspring of an affected person will have a 50% chance of receiving the gene and developing the disease.

The dilemma with Huntington’s chorea is becoming more acute because techniques of recombinant DNA are making it increasingly possible to identify the carrier presymptomatically and before the individual has reproduced. People who are carriers have the option of not reproducing and thus not placing offspring at risk; people who are not carriers can be relieved of a tremendous burden of worry. However, offspring and close relatives may not wish to know that they are carriers and are doomed to come down with the disease. At what age should they be informed? Remember, the disease could be practically wiped out in one generation if carriers did not reproduce. It would certainly be desirable if a potential camer did not reproduce, both from the point of view of society and the emotional stress on such offspring burdened by uncertainty. However, I reject the notion that our society should “oblige” people not to reproduce.

Fetal Screening

his form of presymptomatic genetic screening T involves the fetus. It represents a giant step forward in medical genetics because it permits couples to reproduce despite their risk of having a seriously affected child (eg, Tay-Sachs or Down’s syndrome) and feel secure that the risk has been eliminated.

Noninvasive prenatal screening is done by

measuring maternal serum alpha-fetoprotein and/ or ultrasonography to rule out neural tube defects and other structural defects in the fetus. More accurate screening methods are chorionic villus sampling (CVS) or genetic amniocentesis, which are invasive techniques and therefore are potentially more harmful. The methods can be used for fetal screening of chromosomal abnor- malities or neural tube defects, but, because of possible complications (slight) and cost, they are only used if specifically indicated.

A serious concern is the use of genetic amniocentesis or CVS to identify conditions not serious enough to warrant pregnancy interruption. Certainly, they should not be used as a method to select the sex of one’s offspring.

Screening all pregnant women for maternal serum alpha-fetoprotein is simple and inexpensive and may soon be available. The new recombinant DNA techniques will greatly increase the prenatal diagnosis of many heretofore undiagnosable diseases (eg, muscular dystrophy, phenylketonuria, and cystic fibrosis).

We are thus faced with the possibility that a majority of serious genetic diseases could be diagnosed or ruled out in most fetuses. Obviously, fetal diagnosis for all would be both logistically and financially difficult, especially for the poor. A major ethical problem in this regard is how serious need a fetal problem be to warrant pregnancy interruption? That is best decided by the pregnant woman and her physician counselor.

In summary, the current explosion of new knowledge of genetics has tremendous promise for preventive medicine. What is lacking thus far is an educated society prepared to cope with the ethical problems being posed.

ARTHUR ROBINSON, MD

Arthur Robinson, MD, is a professor emeritus of biochemistry, biophysics, and genetics and professor of pediatrics at the University of Colorado School of Medicine, Boukier. He is alro director of the cytogenetic laboratory at the National Jewhh Center for Immu- nology and Respiratory Medicine, Denver. He received hb MD akgree from Rush Medical School University of Chicago.

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