Extrapolative Genetic Diagnosis in Pre-implantation Embryos
Ben Nafziger
Professor Stan Grove
BIOL410-Biology Senior Seminar
November 14, 2005
Thesis: Recent progress in the field of genetics, specifically the application of extrapolative genetic diagnosis, has generated moral and ethical concerns about the non-medical usage of this recently acquired knowledge.
Outline
I. Introduction
II. Pre-implantation and Pre- and Post-natal Genetic Testing
A. Pre-implantation Genetic Testing
1. Sources of Pre-implantation Genetic Material
2. Functionality
B. Pre-natal Genetic Testing
1. Sources of Pre-natal Genetic Material
2. Functionality
C. Post-natal Genetic Testing Functionality
III. Non-medical Utilization of Pre-implantation Genetic Testing
A. Pre-implantation Genetic Testing and Sex SelectionB. Pre-implantation Genetic Testing and Stem Cell Matching
IV. Conclusion
“Advances in genetics and reproductive technology present prospective parents with an increasing number of choices about the genetic makeup of their children. Those choices now involve the use of carrier and prenatal screening techniques to avoid the birth of children with serious genetic disease, but techniques to choose nonmedical characteristics will eventually be available” (Robertson, 2001, p. 2). In fact, you can already choose nonmedical characteristics such as sex.
Details about pre-implantation genetic testing and selection, as well as pre-natal and post-natal testing for non-medical traits are presented here. A discussion on the ethical and moral implications of this testing will be offered.
Pre-implantation and Pre- and Post-natal Genetic Testing
In 1997, a task force founded by the National Institutes of Health (NIH), Department of Energy (DOE), and Working Group on Ethical, Legal, and Social Implications (ELSI) of Human Genome Research defined genetic testing as, “ The analysis of human DNA, RNA, chromosomes, proteins, and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes or karyotypes for clinical purposes.” Non-clinical uses for genetic testing, such as research, forensic testing, and the testing for non-disease related traits, were excluded from this definition, as the task force’s intent was to “develop generic policies that cover predictive testing for a wide range of medical conditions.” Although ignored in ELSI’s report, the human genome can also reveal, through genetic testing, traits such as sex, physical characteristics, and physiological attributes. Genetic material for extrapolative genetic analysis can be obtained with either pre-implantation diagnosis, pre-natal diagnosis, or post-natal diagnosis (NIH, 1997).
Pre-implantation testing finds its source of genetic material located within in-vitro embryos or oocytes. There are three cell types which lend usefulness to this pre-implantation analysis: polar bodies from the oocyte/zygote stage recovered before karyogamy, blastomeres extracted from cleavage stage embryos, and trophectoderm cells removed from blastocysts (Kanavakis and Traeger-Synodinos, 2005, p. 6). Each of these three cell types provides certain advantages lost to the others. Kanavakis et al reveal that polar body biopsies require the manipulation of oocytes instead of the embryo itself. This is advantageous as it precludes “ethical and safety debates concerning the human embryo biopsy, and the genetic material removed is not destined to become part of the developing embryo” (Kanavakis and Traeger-Synodinos, 2005, p. 7). Cleavage stage embryo biopsies allow for the embryo to be “evaluated morphologically as grade I (correct stage of development, regularly shaped, evenly sized blastomeres, and no fragmentation) to grade III (slow development, unequally sized blastomeres, at least one degenerative blastomere and/or a high level of fragmentation)” (Dawson et al, 1995). Blastocyst stage diagnosis may be advantageous over blastomere or polar body biopsy as “more cells may be removed for analysis, and the biopsy procedure is technically less demanding” and “trophectoderm cells do not contribute to the embryo proper, but form the placenta and other extra-embryonic tissue” (Kanavakis and Traeger-Synodinos, 2005, p. 7). From these three sources, pre-implantation genetic diagnosis can hypothetically be utilized in the detection of any genetic disease (Kanavakis and Traeger-Synodinos, 2005, p. 6). Not surprisingly PGD’s applications are pertinent to non-medical uses as well, including determination of sex prior to implantation.
Genetic material is also available post-implantation or post-conception from pre-natal sources. These sources include trophoblasts, amniotic fluid, fetal cells, and free fetal DNA. Currently, pre-natal diagnosis is preventative in its application and the termination of pregnancy may be the result (Kanavakis and Traeger-Synodinos, 2005, p. 6).
Post-natal genetic testing may also be useful in the predictive determination of genetic diseases. The non-medical functionality is not as much in question since the individual has been born prior to testing. Recent research has uncovered, that some physiological traits may be revealed with this testing, including but not limited to athletic ability (Savulescu and Foddy, 2005, p. 472).
Non-medical Utilization of Pre-implantation Genetic Testing
With access to pre-implantation genetic testing’s capacity to determine sex at an embryonic stage, prospective parents now have the ability to choose the sex of the embryo to be implanted. Between April 1999 and April 2001, thirty-six couples were treated at the Malpani Infertility Clinic in India. All of these couples desired a son. Fourteen pregnancies were achieved and all delivered male infants (Malpani et al, 2002, p. 11). In countries such as India and China, where there is a preference for male children, (Eckholm, 2002, A3), pre-implantation genetic testing for sex may become a popular alternative to pre-natal testing and abortion. There is concern that this sexism will create resultant sex imbalances. As techniques to specify sex have become viable, the ethics involved with preconception sex selection have recently come into question. The main dilemma involves questions of personal freedom in choice versus children being treated as “vehicles of parental satisfaction” (Robertson, 2001, p. 3).
One of the strongest justifications for the use of pre-conception sex selection is its service in the desires of couples who would not have children unless given the ability to choose their child’s sex. Freedom in reproduction “has long been recognized as a fundamental moral and legal right” (Robertson, 2001, p. 4). Can personal choice in reproduction be rightfully limited when there is no social harm involved? It can be plausibly argued that to limit a couple’s right to choose their child’s sex would be a breach in their “procreative liberty” as a couple and unalienable rights as individuals (Robertson, 2001, p. 4). In his paper Preconception Gender Selection, John Robertson lays out an argument for the ethical legitimacy of pre-conception sex selection based on implicit human right. He writes:
They should be free to use a technique essential to their reproductive decision unless the technique would cause the serious harm to others that overcomes the strong presumption that exists against government interference in reproductive choice. Until there is a substantial basis for thinking that a particular use of pre-conception genetic selection would cause such harms, couples should be free to use the technique in constituting their families. (Robertson, 2001, p. 4).
Ethically, it seems that the value of freedom of choice propels the argument for pre-conception gender selection and overrides the ethical quandary of sexism for those in favor of pre-conception genetic selection. This either indicates ones strong belief in freedom of choice or conviction that sex selection is not sexist. In support of a parent’s choice, Dr. Aniruddha Malpani et al states:
We believe that if we allow people to choose when to have babies; how many to have; and even to terminate pregnancies if they inadvertently get pregnant, they should be allowed to select the sex of their child if they would like to do so. The basic purpose of all technology is to give people more control over their destiny than they have had in the past, and we need to allow people to make their own choices for themselves. (Malpani et al, 2002, p. 12).
Arguments against the use of pre-conception genetic selection on the basis of ethics center on several societal concerns. These concerns, as discussed by the Ethics Committee of the American Society of Medicine, include “the potential for inherent gender discrimination, inappropriate control over nonessential characteristics of children, unnecessary medical burdens and cost for parents, and inappropriate and potentially unfair use of limited medical resources...and reinforcement of gender bias in society as a whole” (Ethics Committee, 2001, p. 862).
One of the foremost of these concerns, as noted by Robertson and the Ethics Committee of the American Society of Medicine, is the inherent sexism of allowing parents to choose the sex of their children. In many cultures, where sons are valued more than daughters, parents would use pre-conception sex selection techniques to avoid giving birth to daughters. If this practice became widespread sex-ratio imbalances could result (Ethics Committee, 2001; Robertson, 2001, p. 4).
Ethically, gender selection and sexism seem inherently linked, except in cases of medical necessity. It is argued by Grubb and Walsh in their 1994 manuscript Gender-vending II that any “attention to gender differences” is innately sexist, as perception of variations between the two genders is ingrained in sexist stereotypes. They believe that any offspring gender preferences is necessarily sexist because it values gender difference and thus reinforces sexism by accepting the gendered stereotypes that have systematically harmed women (Grubb and Walsh, 1994). This may not always be the case however, as Robertson remarks, “One could recognize that males and females have different experiences and identities because of their gender, and have a preference for rearing a child of one gender over another, without disadvantaging the dispreferred gender” (Robertson, 2001, p. 4). In this situation, a preference in gender would not constitute sexism, as it would not be denying either gender equal liberties, prospects, or merit as a person. Thus it could be concluded that pre-conception gender selection would be sexist if used because of a belief in the superiority of the male or female sex, but nonsexist if used to yield a male or female because of “parental recognition that the experience of having and rearing a girl would be different then having a boy” (Robertson, 2001, p. 4).
Thus the societal concerns found in debate, both for and against sex or gender selection in the reproductive process, focus mainly on ones definition of sexism and choice. Should a couple’s reproductive liberty be compromised because of inherent sexism in that choice, and is choosing the sex of a child to be conceived even sexist by nature? Does sex or gender affect the “inherent worth” of a child (Ethics Committee, 2001, p. 862)?
As with the ability to access genetic material in the embryo to select for sex, it is also theoretically possible to select for other traits. These may include, but are not limited to traits for physical appearance, certain genetically conveyed abilities, or even similar genetic characteristics to a pre-existing sibling for use as a “compatible donor” of hematopoietic stem cells, organs, or bone marrow (Pennings et al, 2002, p. 534). The last of these practices seems to be the most ethically questionable, as it involves an invasive procedure on a child. In a 2002 submission to Human Reproduction, Dr. Guido Pennings et al discuss this issue in depth beginning with the topic of the instramentalization of the future child:
One of the fundamental rules underlying Western moral thinking is the Kantian imperative. The second formulation of the categorical imperative goes as follows: ‘Act in such a way that you always treat humanity whether in your own person or the person of any other, never simply as a means, but always at the same time as an end.’ (Kant, in Pennings et al, 2002, p. 536).
So is conceiving a child for use as a donor, using the child as simply a means? Pennings et al continues:
It is generally agreed that using someone as a means is not unethical. In fact we do it all the time. An action should only be condemned when it treats a person solely as a means. When does an act instrumentalize a person? Parents frequently decide to make another child as a companion and a playmate for the first one. Is the second child hereby treated as an instrument? (Pennings et al, 2002, p. 534).
It would seem then, according to this argument that the responsibility of an ethical choice falls on the parents seeking a genetic match, or as Pennings states, “The parents’ decision to conceive and select a certain embryo would fail to show respect for the future child if their only reason for creating the child was its tissue” (Pennings, 2002, p. 534). When considering the ethics of this situation, the question seems to be a philosophical one. Is selecting an embryo for post-natal use as a tissue donor using the child as a means or “as an end-in-himself” (Drebushenko, 1991)?
Even if it is concluded that conceiving a child, for use as a donor to a genetically matched sibling, is not using that child as a means, another question arises. Is it ethical to use this child as a donor when informed consent is not possible? An argument can be made that it would actually be beneficial for a donor capable child to be born. There are no physical or medical benefits to be obtained from tissue donation, but some assumed psychological and social benefits could be derived if a child was matched and able to donate successfully. The most obvious example of this would be the ability of the child to grow and have a relationship with its older sibling, hand in hand with saving their life. If the child was unmatched and unable to donate, it would experience the death of its sibling and develop in a family perhaps scarred by this loss. It is generally accepted in society, that growth in an intact family is positive; so would not the ability to donate organs or marrow be positive? (Pennings et al, 2002, p. 536).
Of course, one could take the opposite side of this case just as easily. The argument for the benefits of the selected donor child is based solely on broad moral justifications and inferred benefits for the child. There is no intent on the parents part to benefit the child by selecting for genotype. The physical benefits would be reaped only by the sibling in need of a transplant. Parental concern, in this case, is entirely for the existing child. In ordinary life, parents with more than one child frequently make decisions by which one child is harmed to benefit the other (Ross, 1994). So, “why should the intervention not be against the donor’s interests?” (Delany, 1996; Pennings, 2002, p. 536-537).
Once again, opposing moral philosophies clash in this debate about the welfare of a child conceived as a tissue donor for a sibling. Is moral justification an appropriate substitution for patient consent in cases were consent is impossible to give? Can one assume that donating tissue is in the best interest of the child? If it is not in the best interest of the child, is it morally or ethically acceptable, as parents often make decisions not in the best interest of their children?
Recent advancements in genetics, particularly the application of predictive genetic diagnosis and selection, have generated moral and ethical concerns as to non-medical usage of this recently attained knowledge. These concerns are mostly philosophical in nature, yet they hold the interests of biologists, for their answers will set precedence for accepted ethics in the biological and medical fields in the future. Some techniques, specifically pre-implantation genetic diagnosis, may allow parents control over the genome of their offspring. This is certainly radical to the modern train of thought, but is it ethically immoral to allow? Processes, such as sex selection, certainly could prove negative to society if their use were to become widespread. This can already be seen in India and China, where sex-ratio imbalances are becoming evident after the introduction of more primitive techniques for selecting sex. Should this concern, or others, supersede the liberty now intrinsic to our currently accepted ethical model for reproduction? Western society, especially that which is found in the United States of America, places so much worth on the weight of personal choice and ones ability to make that choice that it is problematic to restrict that choice based on rights granted to an embryo. However, some ethical considerations must be given to the prospects and future of the child selected by its genes. An ethically viable balance between these issues must be attained before pre-implantation genetics can fully be implemented to its potential. As John A. Robertson writes, “Careful ethical analysis and open public debate is essential if new uses of pre-implantation genetic diagnosis are to become acceptable methods for having children” (Robertson, 2003, p. 471).
Works Cited
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Eckholm, E. Desire for sons drives use of Prenatal Scans in China. The New York Times, 2002 June 21: A3.
Ethics Committee of the American Society for Reproductive Medicine. Preconception gender selection for nonmedical reasons. Fertility and Sterility, 75, 861-864)
Grubb, A and Walsh, P. Gender-vending II. Dispatches, 1, 1-3.
NIH, DOE, and ELSI. (1997). Promoting Safe and Effective Genetic Testing in the United States. Retrieved November 7, 2005, from http://www.genome.gov/10001733.
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Malpani A., Malpani A., and Modi D. (2002). Preimplantation for family balancing in India. Human Reproduction, 17 (1), 11-12.
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Robertson, J. A. (2003). Extending preimplantation genetic diagnosis: medical and non-medical uses. J. Med. Ethics, 29, 213-216.
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Savulescu, J, & Foddy, B. (2005). Comment: genetic test available for sports performance. British Journal of Sports Medicine, 39, 472.