By Whitney Stevens & Erica Preiss
"Almost nine months before she was born, Brittany Nicole Abshire passed the most important test she will ever take. Her parents, Renee and David, are both healthy carriers of the trait for Tay-Sachs disease, a cruelly disabling and ultimately lethal inheritable disorder. After they lost one daughter to Tay-Sachs in 1989, they swore they would never have another child unless they could be sure that it would be free of the disease. Genetic tests could diagnose the condition before birth, but the Abshires’ religious beliefs ruled out abortion as a way of screening for healthy fetuses. There seemed to be no hope until the Abshires learned about a new technology called preimplantation genetic testing…"
Scientific technology has advanced to a point where it is possible to analyze the DNA of a pre-embryo before its implantation in the womb. With the development of this process, genetic testing for specific gene combinations has now become a viable option. Those couples at risk of passing on certain heritable genetic diseases reap the greatest benefits of this testing. As with any medical procedure that alters the natural biological processes of life, the artificial selection of genes is accompanied by a variety of both positive and negative responses from today’s society. The varying opinions are the inevitable result of the many ethical and social implications generated by preimplantation genetic testing.
The procedure of preimplantation genetic analysis begins through obtaining pre-embryos by in-vitro fertilization; a process originally developed to assist infertile couples in having children. A woman desiring this preimplantation testing is first required to undergo ovarian stimulation ensuring that more than one egg will be produced. The more eggs capable of being extracted, the greater chance that one of them will test negative for the particular heritable genetic disease. The eggs are then artificially inseminated and allowed to develop to the eight-cell stage at which time a biopsy is possible.
The material to be genetically analyzed can then be extracted from the embryo through a variety of approaches including Polar body biopsy, Blastomere biopsy, and Blastocyst biopsy. These three different methods are each capable of extracting the needed genetic information, but vary in the particular stage of development in which they take place.
The Polar body biopsy is carried out during the first meiotic division of the oocyte, usually within twenty-four hours of the oocyte’s retrieval. This particular technique is used in the testing of heterozygous individuals, where the polar body will have either the normal or mutant allele. The oocyte will have the normal allele if the polar body has the mutant allele and vice versa. The danger of this method is that it is dependent on the absence of crossing over in this first meiotic division, which would result in an oocyte and a polar body which are heterozygous for the mutation.
The preferred approach by many, the Blastomere biopsy occurs three days post- insemination when embryos have reached the eight-cell stage through in-vitro fertilization (see Appendix 1, Figure 1a). One to two blastomeres are then removed for analysis from each embryo without altering its potential to further develop. A fear in this procedure is that blastomere analyses at this stage will not be representative of the whole embryo and possible misdiagnosis may result.
A final approach, the Blastocyst biopsy, takes place further along in the development of the embryo, approximately five to six days after insemination. The embryo at this stage has differentiated into an outer epithelial layer and inner cell mass which later produces the fetus. The benefit of this procedure is that a large number of cells can be extracted from this outer epithelial layer of cells, or extraembryonic tissue, for biopsy. However, less than fifty percent of normally fertilized oocytes can grow to this stage during the in vitro process.
Whatever the method of biopsy utilized, the information obtained must be manipulated to allow genetic analysis at the single-cell level where mutations can be detected. The two major technologies employed for this single-cell genetic analysis include the polymerase chain reaction (PCR) and fluorescence in-situ hybridization (FISH).8
PCR begins with the denaturing of the DNA specimen previously extracted through biopsy. An increase in temperature induces the breakage of hydrogen bonds holding the two DNA strands together, thus resulting in their separation. Next, the temperature is decreased to allow the primers, or temperature-stable reagents, to anneal to complementary sequences on opposite strands of DNA. Primers in this case mark the ends of the segment of amplified DNA. Finally, the new nucleotide strands are produced through extension from each annealed primer using the single-stranded DNA as a template. The process is repeated until the obtained PCR product is deemed sufficient for analysis. The necessary amplification can take place in a few hours, and the amount of target DNA acquired should be enough to enable rapid screening for the presence or absence of the mutation. Screening is made possible by a variety of different methods, including digestion of PCR product through restriction enzymes followed by gel electrophoresis analysis (see Appendix 1, Figure 1b).
The latest and most widely utilized technique, FISH, involves spreading out single embryonic nuclei on microscope slides. The in-situ hybridization of these nuclei is made possible with the use of fluorescently labeled probes that are chromosome-specific. These particular probes produce different color signals for each chromosome tested. The advantage of the FISH technique is that as many as five different chromosomes can be detected, allowing for detection of single allele differences at the single cell-level, allowing more extensive screening than the PCR method permits (for example, the screening of sex chromosomes).
The process of preimplantation genetic testing is then completed with the transfer of all embryos diagnosed as unaffected into the uterus. Confirmation of normal pregnancy is soon required through amniocentesis, and follow-up studies are later done on children who have undergone preimplantation genetic analysis.
Preimplantation genetic diagnosis is a viable option for couples with a family history of heritable genetic disorders. Unlike most couples who undergo in-vitro fertilization, most couples who utilize preimplantation genetic diagnosis do not have fertility problems. The process allows couples the opportunity to avoid the burdens that come with raising a child with a serious genetic disease. The costs, both financial and emotional, can be enormous. For instance, children born with Tay-Sach’s disease, a disabling condition that results from the lack of an enzyme that breaks down fatty substances in the neurons, rarely live past the age of five. The family is subjected to witnessing the extremely slow and painful death of a child. As for the financial burden, one can take the example of a family caring for a child with cystic fibrosis. The average lifetime cost of caring for a child with this condition is estimated to be upwards of one million dollars (see Appendix 2, Figure 2a). This is an enormous price to pay for the majority of the population. Prenatal testing is an option, but in this case, if the fetus tests positive for a certain disorder, the couple is forced to make the difficult decision of whether or not to abort the pregnancy. Because of this, many couples are faced with moral conflicts that stem from both their personal and religious beliefs. By testing an embryo before it is implanted, many couples are able to sidestep the moral and ethical dilemmas that are posed by abortion. If an embryo tests positive for a certain disorder, it simply does not have to be implanted in the mother’s womb.
Many people fear that differing opinions of what constitutes a serious genetic condition is likely to become a serious problem. According to the Nuffield Council on Bioethics, serious genetic disorders are defined as "conditions which are life-threatening or seriously handicapping, and for which treatment is either not available or unsatisfactory". In one European study, a conference of medical professionals was given a survey and asked to classify a certain genetic disorder as lethal, serious but not lethal, or not serious. The surveys were collected and it was found that different medical professionals had classified the particular condition under all three categories. For instance, albinism is a condition that results in a lack of pigmentation. It is not a disease itself, but it creates a higher risk for certain types of cancers and it is associated with bad vision. If the gene for albinism is identified, should couples be able to opt not to have a child with this condition?
The central moral issue in the debate over preimplantation genetic diagnosis focuses on the status of the pre-embryo. There are three different perspectives on this issue. The first view regards the pre-embryo as a part of the mother’s body, a collection of undifferentiated cells not yet constituting a human life. According to this view, the mother has the right to have this pre-embryo tested for any genetic abnormalities and to choose, after receiving the test results, whether or not the pre-embryo should be implanted. The second viewpoint holds that the pre-embryo is a human being because it has a new genotype that was created upon conception. The pre-embryo has its own individual rights, to which the rights and wellbeing of the mother are irrelevant. The third viewpoint, which is generally accepted by today’s society, states that the pre-embryo is a potential human being whose rights should be respected as long as they do not interfere with major social or maternal interests.
Further problems arise because it is difficult to reach a general consensus as to when the status of potential human being should be given. Once again, there are three different opinions. Some believe that the status is achieved upon conception, others believe that it is achieved upon implantation, and still others believe that it is achieved when the "primitive streak", which establishes the beginning of cell differentiation, appears. Many ethical issues dealing with preimplantation genetic diagnosis have been solved by the acceptance of the "primitive streak" definition.
There are conflicting opinions as to the morality of preimplantation genetic diagnosis that are based on different religious beliefs. As a general rule, most religions seem to relate their views on the subject to their views on abortion. In the Jewish faith, the fetus does not become a human being until after birth and many rabbis refer to the fertilized egg as simply "fluid" up to as many as forty days after conception. The embryo does not have a soul and, therefore, it can be disposed of. By this reasoning, if an embryo tests positive for a genetic abnormality, disposing of that embryo does not violate any element of the Jewish faith.
On the other hand, the Roman Catholic faith views that the fetus has been a human being since the moment of conception. Therefore, preimplantation genetic diagnosis is not an acceptable practice and if one decides to dispose of an embryo because it tests positive for a certain genetic disorder, it is seen as ending a human life. Other denominations of Christianity do not view the embryo as a human being and have no objections to preimplantation genetic diagnosis.
The use of preimplantation genetic diagnosis to choose the sex of an embryo is already being practiced at multiple centers throughout the world. Should couples be able to choose the sex of their children? A proposed framework for answering this question includes the following stipulations: a couple may not choose the sex of their first child, they may not choose the sex if there is already an equal number of male and female children, the sex which the couple chooses must be the less represented in the family, and finally, the aforementioned restrictions are nullified when dealing with the avoidance of certain sex-linked genetic diseases, for example hemophilia.
Another ethical consideration is the dispute over what is considered normal versus abnormal. It is estimated that everyone carries between five and ten genetic defects. If, by chance, one meets another person with the same genetic defect that condition could manifest itself in their offspring. Whether or not people view that condition as a problem is a source of conflict. For instance, when surveyed, fifty-five percent of the deaf population thought that genetic testing would do more harm than good and forty-six percent thought that the use of genetic testing understated the role of deaf people in today’s society. In fact, those who supported preimplantation genetic testing stated that they would be more likely to use it to have deaf offspring rather than to avoid having deaf offspring (see Appendix 3, Figures 3a – 3e).
In countries such as the Netherlands and Germany, organizations of handicapped people have stressed the "right to abnormality" and have emphasized the role that handicapped people play in contributing creativity and diversity to society. Germany, because of its past during the years of Hitler’s dictatorship, is even hesitant to discuss the implications of preimplantation genetic testing because many fear a situation similar to the one during World War Two in which Hitler aimed to create a "master race" through the manipulation of genetics. Ireland, with its strong religious beliefs, has questioned the value of defining some characteristics as normal and others as abnormal, "especially when those definitions may have implications for the protection and nurturing of human lives".
In addition to the ethical considerations surrounding preimplantation genetic analysis, the societal implications of such testing must also be addressed. Society in general is largely uneducated about the principles of genetics and genetic testing. In the early 1970s, the federal government funded a screening program to detect carriers of the gene for sickle cell anemia. The general public was uninformed about the meanings of the results of the tests, and many perfectly healthy carriers were led to believe that they were sick. In addition to this, many carriers were denied health insurance coverage. In some cases, state legislatures even passed laws mandating the testing of children for the defective gene before school enrollment. Although this does not qualify as an example of preimplantation genetic diagnosis, the results may foreshadow similar consequences that could arise from this procedure.
There is a margin of error in preimplantation genetic diagnosis, as exists with all genetic testing. Excessive testing has the possibility to do harm, causing parents to worry unnecessarily. One study examined the effects on families whose children initially tested positive for cystic fibrosis and later proved to be healthy. Despite proof of the misdiagnoses, one-fifth of the parents continued to worry that their children had the disease. Experts have expressed concern about "how stigmatizing children with a disease label may warp personal development".
Unfortunately, our genes do not belong exclusively to us; they are shared, in part, by our parents, siblings, and offspring (see Appendix 4, Figure 4a). A 1992 March of Dimes poll found that "fifty-seven percent of the public thinks someone other than a patient deserves to know if he or she carries a defective gene" (see Appendix 4, Figure 4b). Even a majority of physicians have displayed a willingness to violate patient confidentiality and inform relatives at risk in the case of genetic diseases such as Huntington’s. Insurance companies contend that they need this information to set fair rates for all policyholders. They believe that this does not constitute discrimination, but rather that it would be wrong to make healthy policyholders pay more to cover those with certain genetic disorders (see Appendix 4, Figure 4c).
At this point in time, the aims of preimplantation genetic testing remain, for the most part, admirable. The benefits of such testing are generally constrained to the elimination of "serious" genetic diseases. However, the genetic technology will inevitably develop to the extent where it is humanly possible to engineer a desired physical appearance for your child before the embryo has even been implanted. There is no way to ensure society will make mature and responsible decisions when technology evolves to this degree. Today’s society continues to view disabilities as a negative rather than positive aspect of the world we live in. We must consider the idea that genetic imperfections contribute to diversity and make us what we are – that is, human beings. After all, if people had been eliminated or disregarded on the basis of genetic defects, there never would have been an Einstein, a Lincoln, a Darwin, or a Beethoven.
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