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days after fertilization |
One of the most exciting new technologies for prospective parents is preimplantation genetic diagnosis, or PGD. The procedure involves testing embryos before they are implanted in the uterus, thus giving parents the ability to choose from a selection of their own embryos before a pregnancy even occurs. Couples who know they are at high risk of producing genetically disadvantaged offspring would be able to carry a carefully selected embryo to term, confident that it will be a normal healthy baby. Further, a woman who chooses to begin a family later in life, and whose children would therefore be at higher risk for certain genetic abnormalities, could ensure that an embryo is healthy before implanting it in her womb. As with most technological advances, there is the potential for abuse. However, the benefits of PGD far outweigh the risks.
The procedure was originally designed for couples in which both husband and wife are carriers of an autosomal recessive genetic disease. That is, both husband and wife have one normal allele and one allele that codes for the disease; they are heterozygous for that gene (5). Mendelian genetics tells us that such a couple has a one in four chance of producing an affected child (Figure 1).
One example of an autosomal recessive disease is Tay-Sachs, an incurable disorder for which about one in every thirty American Jews is a carrier. The symptoms of Tay-Sachs first appear about 6 months after birth when an apparently healthy baby gradually becomes paralyzed and loses mental abilities. Children afflicted with Tay-Sachs do not live to be more than five years old. In one congregation in New York City, the tragic disorder was so prevalent that the rabbi refused to conduct a marriage ceremony until the couple had genetic testing done to determine whether they were carriers. PGD could be a godsend for couples in such a situation who want a healthy child who is biologically theirs and don’t want to face the possibility of an abortion after amniocentesis later in the pregnancy.
PGD usually relies on in-vitro fertilization (IVF), a solution for infertility that has not yet been perfected. In standard IVF, eggs are removed from a woman surgically, fertilized in a laboratory dish, either naturally or by injection, and then reimplanted in her body. IVF has only limited success rates and involves a barrage of hormone treatments for the woman prior to the removal of eggs (5). The hormone cocktails differ slightly from lab to lab, but the purpose is always the same –to induce the ovaries to release multiple eggs. This is crucial because placing more than one embryo significantly increases success rates; chances are that at least one of the embryos will implant (9).
However, there are major problems with both superovulation and the transfer of multiple embryos. Superovulation often causes immature or low quality eggs to be released, which results in more miscarriages (9). The drugs may also affect endometrial development. Multiple implantation increases the chance of multiple pregnancies, miscarriages and prematurity, all of which can be emotionally and psychologically traumatic for the couple (9).
In order to decrease such adverse effects and increase pregnancy rates, scientists have experimented with different ways of conducting PGD. The viability of the embryo generally decreases the longer it is out of the body due to inadequate culture media, so the standard approach has been to remove a single cell from each embryo as soon as possible (9) . This is generally two or three days after fertilization, when the embryos are made up of four to eight cells called blastomeres (3). On the other hand, when there is a healthy five or six day old blastocyst, its chances of survival are better than those of the two or three day old embryo (6) (see Figure 2). The newest approach to this problem is to allow natural in vivo fertilization and then retrieve the embryos by flushing the uterus in a process called uterine lavage (6). This way, the embryos are stronger because they are out of the body for a shorter period of time (1). Finally, each embryo is held in place by suction and the zona pellucida, a protective membrane surrounding the early embryo, is punctured with a sharp instrument or an acid probe. A blastomere is aspirated through the puncture and the DNA is isolated for testing (3, 5).
The tests may vary, depending on the type of disorder and its location on the genome. In the case of x-linked disorders (those associated with the X-chromosome), the at-risk males are simply discarded (3). Scientists use a method called fluorescent detection of in situ hybridization (FISH) to look for chromosomal abnormalities like trisomies (extra chromosomes) (9). In FISH, colored probes are used to determine the presence or absence of a specific region of a chromosome. For defects of a single gene, a specific segment of DNA is amplified by PCR (polymerase chain reaction), making it possible to find even single nucleotide (9).
The ingenious new technology of PGD has been hailed by some as the end of genetic disorders, but there are still many questions to be answered. In addition to the numerous technological difficulties, there are significant ethical considerations. For the most fervent pro-lifers, PGD is unthinkable. Abortion, they might say, only kills one baby at a time while PGD might eliminate eleven or twelve embryos for every baby it produces, depending on how many eggs were harvested (2). That the mother is not technically pregnant and that the embryos are often as small as four cells would be irrelevant to such an argument.
More moderate pro-lifers and advocates of choice might look at the issue from the opposite perspective, saying that PGD would prevent the use of traditional abortion in cases of genetic abnormality (8). For an at-risk couple unwilling to bring a genetically defective child to term, PGD is far less emotionally traumatic than a traditional abortion. PGD is perhaps more acceptable to some people than abortion because of a belief in morality as a question of degree; preventing implantation is acceptable, abortion is better earlier than later, and infanticide is wrong (2, 7).
Aside from the argument of fetal rights versus parental rights, ethicists are raising a number of other relevant questions. For example, what would be the effect of PGD on the status of people with disabilities? Would the expectation of perfect children lead to the alienation of the disabled? Jeffrey Botkin argues that it would not. "despite the use of prenatal diagnosis for several decades… individuals with disabilities have never had more social support than they do today" (2). Botkin points to the Americans with Disabilities Act to support his argument, but then he goes on to qualify this by suggesting that a distinction may be made in the future between those disabled from preventable conditions and those suffering from unavoidable causes.
[PGD] could promote societal expectations of "perfectibility" in children, thus fostering a more narrow intolerance of those disabled from genetic and congenital etiologies and, perhaps, of the parents who choose to have such a child (2).
I feel, however, that this would be an effect of widespread amniocentesis as well. If it has not happened despite decades of amniotic testing, perhaps people feel that every situation is different; one can make the decision not to raise a child with Down’s syndrome and still respect the family that is strong enough to do so.
The final and by far the most terrifying argument against PGD is that, in the distant future, it will lead to widespread selection for frivolous traits. In a Huxley-esque society rooted in eugenics, parents might go to a clinic and request only the intelligent, heterosexual, well-built, brown-eyed male embryos - that is, assuming genes were found for such traits. Dr. Botkin ponders the effect of such selection on parent – child relationships.
If frivolous selection were to occur even on a small scale, I am convinced it would have disastrous effects not only on parent – child relationships, but also on all human relations. We would no longer feel equal in our status as human beings. Instead, there would be insurmountable distinctions made between us. At the same time, I do not believe PGD will lead to eugenic selection. Selection against diseases and selection for eye color are two completely different prospects. There is no reason to believe that, once we take the first step, there is no escaping the "slippery slope". We can and should restrict the applications of PGD to life threatening or debilitating diseases.
As scientists unravel the mysteries of life, our abilities are quickly approaching the realm of science fiction. The difference between what we can do and what we should do has never been more controversial than it is today. Some seem to think that the easiest and least frightening solution is to put a halt on all genetic research. This is both impossible and unethical. We should not deny people the healthy families they desire out of fear that the technology may be used improperly later. Such arguments are analogous to denying early humans fire because it would later be used to burn people at the stake. The fault is not with the one who discovered fire, but with the society that misused it centuries later. For this reason, it is crucial to think about the possible misuses now, before they become standard practice. If we are cautious, we will use science and technology as Aldoux Huxley suggests in the foreword of Brave New World: "as though, like the Sabbath, they had been made for man, not (as at present and still more so in the Brave New World) as though man were to be adapted and enslaved to them (4).
This is a punnet square that predicts the likelihood of a couple having a child with a certain trait. The parents genotypes are outside the square and the possible progeny are inside the smaller squares. ‘A’ is dominant and ‘a’ is recessive. If aa codes for the presence of a disease, these parents have a one in four chance of having a child with the disease.
days after fertilization
1. Advanced Fertility Center of Chicago, "Advanced Fertility Web Site" <http://www.advancedfertility.com/>
2. Botkin, Jeffrey R., "Ethical Issues and Practical Problems in Preimplantation Genetic Diagnosis", Journal of Law Medicine and Ethics, 26:1 (1998)
3. Fackelmann, Kathy A., "Test-Tube Diagnosis", Science, 146 (1994)
4. Huxley, Aldous. "Brave New World", Harper and Brothers, England, p. ix (1932)
5. Reinhardt, Veronica, "Genetically Correct: Ensuring Perfect Babies", Discovery Communications Inc., (1997)
6. Simpson, Joe Leigh and Sandra Ann Carson, "Preimplantation Genetic Diagnosis", The New England Journal of Medicine 327:13 (1992)
7. Turner, Frederick, in "Forum", Harper’s Magazine, November (1992)
8. Vines, Gail, "Every child a perfect child?", New Scientist, 148 (1995)
9. Winston, Robert M.L. and Alan H. Handyside, "New Challenges in Human in Vitro Fertilization", Science, 260 (1993)