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McKenzie Frey Dr. Schnee and Dr.

Idziak Human Genetics and Ethics & New Genetics October 9, 2012 Designer Babies and Intelligence Certainly parents aspire to provide the best possible lives for their children. Of course, many parents would jump at any opportunity to determine the physical performance or musical ability of their children, but parents would especially pursue the opportunity to offer their children a boost in intelligence such as determined by the HMGA2 gene. Thanks to a method called Pre-implantation Genetic Diagnosis, or PGD, parents now possess the ability to do exactly thatrefer to science for the selection of desired traits in their offspring. Discovered after the completion of the Human Genome Project in the early 1990s, scientists found that by extracting one cell from an eight-cell human blastocyst, or embryo, they could test the genetic makeup with the use of polymorphic markers (Chang, et al., 2011). These polymorphic markers have short tandem repeats (STRs) that are helpful to analyze the genotype of the tested cell (Chang, et al., 2011). This process of PGD allowed doctors and scientists to recognize whether an embryo was affected by certain diseases. However, recently PGD has become a means for parents to select desired, non-medically-related traits, such as intelligence, in an attempt to create designer babies (Agar, 2006). Is it ethically permissible for parents to utilize PGD in order to attempt to determine and select traits, specifically, regarding their childrens intelligence? I will argue that it is not ethically permissible for parents to select the traits of their children in non-medically-related scenarios by using intelligence as an example. I will support my position using the ethical theory of Utilitarianism.

According to several Molecular Medicine authors in an article regarding HMGA2 Gene Expression, the HMGA2 allele is strongly expressed in the early stages of fetal development and can be located in all embryonic cells (Chau 2003). However, during later stages of fetal development, HMGA2 becomes restricted to particular cell types and ultimately ceases to increase just before birth (Chau 2003). Recently, scientists involved in Project ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) have found that effects of the HMGA2 allele have caused larger brain sizes and higher IQ scores in individuals (ABC Science 2012). According to researchers at the University of Bristol, individuals typically express the homozygous genotype of TT, which indicates average height and intelligence. However, individuals expressing the rare, homozygous genotype CC have been statistically determined to be taller and appear to perform better in school tests [and] have higher IQ (von Hinke Kessler Scholder, et al., 2010). In April 2012, a team of more than two-hundred scientists from one-hundred different institutions worldwide came together to map the genes which boost or diminish brain size and intelligence in a study called Project ENIGMA (ScienceDaily 2012). These scientists studied over 20,000 healthy human subjects, evaluating each of their brain sizes from MRIs while simultaneously screening their DNA (ScienceDaily 2012). Professor of Neurology at the David Geffen School of Medicine at UCLA, as well as member of the UCLA Laboratory of NeuroImaging, Paul Thompson, announced that people who received multiple Cs from their parentsscored on average 1.3 points higher on standardized IQ tests than those within the population with only one C in the HMGA2 [allele] sequence (ABC Science 2012). Thompson articulates that, While the effect [of increase in standardized IQ tests are] small, [they] would helpbrain[s] resist cognitive decline later in life (Duel, 2012). The ENIGMA team found that

every T [nucleotide] in place of a C [nucleotide] represented a 0.6 percent smaller brain (ScienceDaily 2012). While the HMGA2 gene appears to establish brain size and IQ scores, as well as provide individuals with increased height, it is also known to cause brain disease and promote mental illnesses, such as late-onset Alzheimers disease and Schizophrenia (ScienceDaily 2012). Originally established to detect and avoid serious genetic conditions (Davis 2006), Geneticists use PGD to extract one or two of eight cells from a two to four-day fertilized embryo in a procedure called cleavage-stage biopsy (Chang, et al., 2011). In cleavage-stage biopsy, scientists have found the genotyping success rate to be about seventy-five percent accurate (Chang, et al., 2011). DNA sequencing and the use of polymorphic markers detects the location of the HMGA2 gene variation and scientists compare the HMGA2 sequence to that of the human genetic code found from the Human Genome Project (Chang, et al., 2011). Geneticists then examine the DNA sequence of HMGA2 in order to determine the number of T versus C nucleotides (ScienceDaily 2012). Depending on the sequence of the HMGA2 gene, geneticists can determine the level of intelligence embryos express. Thus, scientists implant selected blastocysts into the female uterus, completing the process of HMGA2 trait selection. However, while this procedure appears successful in attributing proper gene selection, PGD is an expensive procedure, costing on average about $12,000-16,000, with a likelihood of a successful pregnancy resulting in a live birth [at] about thirty-seven percent per cycle (Davis 2006). Utilitarianism assesses the consequences, both positive and negative, for each person involved in an ethical scenario and considers the greatest consequences to be the determining factors of whether something, in this case PGD for trait selection of non-medical features HMGA2, should be ethically permissible. Many arguments against the use of PGD have

considered the practice to be unethical in regards to selection of desired, non-medically related traits. For instance, one argument emphasizes the fact that the procedure is not one-hundred percent guaranteed to accurately select the desired trait of intelligence, and even if the trait is accurately selectedessentially, 1.3 points scored higher on standardized IQ tests only means that one would correctly answer a few more questions than the average individual (Duel, 2012). While PGD acts as a detector for serious genetic diseases, this procedure can still produce a misdiagnosis, especially regarding the HMGA2 gene, due to the trait being newly discovered and non-medically related. According to Wilton et al, diagnosis from a single cell remains a technically challenging procedure and the risk of misdiagnosis cannot be eliminated (Wilton, et al., 2008). While about ninety-nine percent of DNA is identical in every individual human, locations called polymorphisms appear to display individual variations of nucleotide bases on the DNA sequence (von Hinke Kessler Scholder, et al., 2010). Thus, the importance of the polymorphic markers with short tandem repeats (STRs) become significant in order to prevent the misdiagnosis of desired alleles because they are to link to the appropriate amplified alleles (Chang, et al., 2011). The Childrens Oncology Group estimated [the] error rate of gene expression found during PGD to be less than five percent (Davicioni, et al., 2009). However, misdiagnosis of allele variations may occur in PGD due to maternal or paternal contamination, ADO, or allele drop out, and chromosomal mosaicism, or the false portrayal of a selected trait (Chang, et al., 2011). Allele drop out (ADO) occurs when one of the alleles fails to be amplified, which may lead to the transfer of misdiagnosed embryos (Chang, et al., 2011). Utilitarianism considers the problematic flaw of PGD misdiagnosis in terms of its consequence for both the parents and the child. For instance, while parents intend to spend thousands of dollars to ensure their child has the rare allele variant of the HMGA2 gene, the five

percent rate of misdiagnosis does not guarantee one-hundred percent accurate results (Davicioni, et al., 2009). One consequence resulting from a misdiagnosis may appear if the child fails to express the desired level of intelligence the parents have anticipated. In example, the childs parents may feel disappointed at having spent thousands of dollars to test for the HMGA2 gene when or if the child appears to lack desired intelligence. Likewise, a greater consequence may result if parents express resentment toward the child for his or her inability to exhibit the 1.3 point increase on standardized IQ tests. However, if parents do not recognize the childs lack of desired intelligence, they may end up pushing the child too hard in school, feeling that the child should live up to the above-average expectations of intelligence, such as that of a child with proper HMGA2 gene diagnosis. Greater than of all these consequences, if parents are highly unsatisfied with their childs apparent lack of intelligence, the child may feel incapable of rising up to his or her parents set expectations and as a result may feel disappointed in and resent him- or herself. However, if PGD accurately diagnoses the child, positive consequences may result in that parents may not solely centralize on the childs superior intelligence without acknowledging other traits he or she exhibits, such as acute musical or athletic ability. As for the child, even if a misdiagnosis occurs, he or she may still exhibit above-average intelligence scores, which would allow the child the opportunity to express his or her own talent in a natural way. Also, if the child expresses a phenotype with above-average height, he or she may exhibit increased intelligence, as well as excel in sports and other extra-curricular activities. In this case, according to Lawlor et al, the child may display more social confidence and make friends easily, may have stronger competitive characteristics that help him or her excel in his or her out-of-

school activities, and may ultimately acquire a higher sense of self-esteem (von Hinke Kessler Scholder, et al., 2010). Although proper HMGA2 diagnosis appears beneficial to the child in allowing him or her to exceed beyond intelligence required in order to do well in school, the five percent possibility that the child may be misdiagnosed due to contamination or being a chromosomal mosaic exists (Wilton, et al., 2008). If the child is misdiagnosed and his or her IQ scores show results lowerthan-average, or if the child exhibits a mental disability, parents may forever resent undergoing the PGD procedure at all. This outcome would increase the hardships and disappointment of parents, especially if they already used a large sum of money to have PGD utilized for trait selection of HMGA2 and realized they need that money to care for their disabled infant. In addition to the possibility of a misdiagnosis for HMGA2, Utilitarianism considers the positive and negative consequences of children who have been selected and born naturally previous to parents utilizing PGD to select for the intelligence trait. According to J.A. Robertson, it is ethical to consider whether selection [of particular traits, such as HMGA2] carries amessage about the worth of existing groups who have been naturally selected at conception (Robertson 2003). While PGD allows parents to give their children an early boost in life by genetically selecting the HMGA2 gene for increased intelligence scores, those children born previous to PGD siblings would not only face the possibility of being intellectually disadvantaged, but may also struggle emotionally and encounter hardships mentally in regards to their parents, PGD siblings, and themselves (Agar 2006). For instance, one consequence considers the naturally-born siblings of PGD children in that they may feel that their mother and father exhibit a sense of favoritism toward their HMGA2 selected sibling, because he or she has been ordained with superior intelligence. The parents distinguished favoritism may lead to the

greater consequence that the naturally-born siblings may feel a sense of competition towards the PGD sibling as they each age, in which the children may centralize on determining which individual, naturally-selected or PGD-selected, can gain their parents true approval and love. Greater, still, arises the consequence that the child born through natural selection may not feel capable of performing 1.3 points higher on standardized IQ tests and may exhibit a shorter phenotype which would not allow them the advantage of excelling in sports or other extracurricular activities. Due to these feeling of inadequacy, the naturally-selected child may resent themselves, feeling that they are flawed, or may even become obsessed with finding some way to attain his or her parents approval. While PGD may provide parents the opportunity to genetically provide children with an advantage intellectually, Anne-Marie Abardo argues in her article, Designer Babies: Creating Perfection or Breeding Trouble, that in order to give children an educational advantage, parents [could] try to send [them] to preschools and elementary schools at an early age (Abarado 2009). By sending their children to school at an early age, parents would offer their children the advantage of achieving 1.3 points higher on standardized IQ tests in a natural way. Likewise, Dr. Thompson argues, If people wanted to change their genetic destiny they could either increase their exercise or improve their diet and educationmost other ways we know of improving brain function more than outweigh this [HMGA2] gene (Duel, 2012). Therefore, utilizing PGD to select for genetic intelligence appears unnecessary. Parents with financial advantage may already be able to send their children to prestigious schools in order to challenge and expand the childs knowledge. However, by utilizing PGD to select for an above-average intelligent child, the parents are also subjected to negative consequences, such as those involving the mothers in-vitro fertilization, which presents the

probability that the child may fail to implant in the mothers uterus, and of those consequences involving the mental and emotional trauma of the father if the child does not survive to full term. According to Davis, there is a seventy-three percent chance the child will carry to full-term and survive after PGD and IVF (Davis 2006). Utilitarianism considers the greater consequences for both the mother and father in this case, such as if the child dies, the mother, as well as the father, will be devastated at the loss of the child. The parents may not only be subject to endure their grief at the loss of their unborn child, but they may regret spending the thousands of dollars invested to the PGD procedure to test for the HMGA2 allele. In addition to the consequence of both parents feeling loss, grief, and disappointment, a greater consequence may arise if the parents suffer to the point that neither is capable of comforting one another, which may lead the couple to decide to divorce. In an article written by Davis, she states, risks [of PGD] to the resulting babies are not yet known, although there [are]risks to the mother (Davis 2006). These risks include ectopic pregnancy, or pregnancy outside the womb, and ovarian hyperstimulation syndrome, or complications due to some forms of fertility medication. In an ectopic pregnancy, the child may be incapable of surviving to full-term without a proper uterine environment. In addition to these consequences involving the fetus or infant, the mother may be subjected to undergo surgery in order to remove a potentially deceased child from her body. As with all surgery, complications may arise and might result in the death of both mother and child. Due to these risks toward the infant and mother, the negative consequences automatically outweigh any positive consequences in this scenario. The consequence of parents using PGD to select the HMGA2 gene for their children may be incapable of accepting the natural traits and flaws of the child. For instance, Davis argues that

parents [may become] so fixated on the importance of [the selected trait], [that they] will find it extremely difficult to be open to the childsnatural direction (Davis 2006). An example of this might be exhibited by the parents anticipation that their child may use their intelligence to become highly involved in politics and law, thus the parents may highly encourage their child to become a legal representative of the law or even pressure them to attempt to become president of the United States. However, the child may not display an interested in seeking the dreams of his or her parents and, instead, may aspire to become a star athlete, artist, or musician. In addition to parents struggling to cope with the natural flaws of their PGD-selected children, they may also set high expectations for their child to succeed academically. If the child fails to meet these expectations, consequences for both parents and the child arise. For instance, parents may believe the 1.3 point increase in standardized tests to mean that the child has significant increase in intelligence. However, parents may be disappointed to realize the increase is not as significant as they had hoped for due to the 1.3 point increase being the result of an individual answering two to three more questions correctly on a test (Duel, 2012). Thus, parents may set high standards of achievement for their children, because they feel the child possesses a superior HMGA2 allele. Therefore, consequences arise regarding both parents and child if the child makes unintelligent mistakes in life which could have been resolved through intelligent thinking and processing. For instance, the parents may be severely disappointed in the child and without considering environmental factors such as peer pressure and a childs desire to fit in with friends, they may resent him or her for making unintelligent mistakes at all. The parents resentment may reflect poorly on the child, causing him or her to resent him or herself and doubt his or her own intelligence. Likewise, the child may project his or her resentment towards his or

her friends for feeling that they helped he or she to make the mistake that disappointed his or her parents. Bioethicist, Ronald M. Green states in his book, Babies by Design: The Ethics of Genetic Choice, that he believes humans should begin considering deliberate interventions in our own childrens genetic makeupto both prevent disease and enhance human life (Green 2007). Therefore, while high parental expectations may pressure the child to excel intellectually, positive consequences arise for the child if he or she is capable of achieving those expectations. For instance, the child may excel academically because the HMGA2 trait for intelligence may promote his or her welfare. An example of the childs promoted welfare includes the potential that the gene may make it easier for the child to do school work, which could allow the child to pursue other interests such as sports or music. As the child ages, their intelligence may allow them the opportunity to prosper in job opportunities in which intelligence would allow the child to become more successful in our technological society. If the child were to become successful enough to invent or discover something new in his or her career choice, he or she may improve or enhance the status of society as a whole. While PGD may appear beneficial towards selection for children exhibiting genetically desirable intelligence, and while the rare homozygous HMGA2 gene may allow the promotion of the childs welfare, the HMGA2 gene is also highly known to cause brain disease and promote mental illnesses, such as late-onset Alzheimers disease and Schizophrenia (ScienceDaily 2012). While parents utilize PGD with the intend to select for the rare homozygous HMGA2 allele and with hopes to provide their children a boost in intelligence, the negative consequences of these late-onset diseasessuch as loss of memory or severe paranoia and delusionpose severe threats to the future wellbeing of the child. For instance, the child may excel intellectually, but,

as he or she ages past retirement, their memory may slowly deteriorate from late-onset Alzheimers disease. Consequently, the PGD candidate may be subject to damage of his or her long- and/or short-term mental health and may fail to voluntarily recall past memories, events, or important friends and family. Greater than the consequence of acquiring Alzheimers disease and involuntarily forfeiting once-meaningful memories, the family of the PGD candidate may suffer if the late-onset disease causes their mother, wife, husband, father, etc. to be incapable of recognizing important family members, such as a wife, children, and possibly even grandchildren. Due to the severity of Alzheimers disease, the PGD candidate suffering from the mental illness may be subjected to join an assisted living environment, which could increase the negative effects of the disease. Likewise, if the child is affected by late-onset Schizophrenia, he or she may be incapable of exhibiting proper intellect and, if employed, may be subject to forfeiting his or her career. Further, if the symptoms of late-onset Schizophrenia present paranoia, hallucinations, or other delusions, the effects of the disease may cause the individual to have difficulty in keeping close friends and other loved-ones outside the realm of his or her immediate family members. Additionally, if the Schizophrenic symptoms appear too severe to the point where he or she is inflicting physical self-harm, the individual may need to be cared for by relatives, possibly siblings or even his or her parents who may be well-near needing living assistance themselves. If the individuals Schizophrenic symptoms cause him or her to inflict physical harm towards others, he or she may need to be rehabilitated to a mental institution, which may cause the effects of the disease to increase further. Ultimately, Utilitarianism would consider the use of PGD to specifically select for the HMGA2 gene to be unethical. Utilitarianism would agree that genetic selection for the

intelligence gene would be unnecessary based on the arguments Agar and Thompson provide that suggests parents could provide their children the intelligence advantage without utilizing PGD, but by sending them to school at an early age and improving the childs diet, education, and exercise (Duel, 2012). In addition to healthy living, eating, and educating habits, the negative consequences outweigh the positive consequences for the scenario of using PGD to select for desired traits such as HMGA2. Regarding the parents and child involved in a misdiagnosis during PGD, though the error rates may only be five percentwith no way to completely eliminate the risk of misdiagnosis, the consequences imply that the parents may face financial disappointment and may potentially resent their child for his or her incapability to display the desired intelligence (Wilton, et al., 2008). Here the consequences appear more severe and detrimental to the mental and emotional health of the family as a whole. Likewise, naturalborn siblings of PGD selected children face greater consequences of feeling low self-worth and may face self-resentment at being incapable of achieving IQ standards of their siblings. These natural-born siblings may also resent their PGD-selected siblings and the competition of winning their parents approval and love may harm the relationship of the siblings, as well as the mental and emotional stability of the family as a whole. In addition to these negative consequences, the thirty-seven percent chance that the child may not implant into the mother and survive to full term produces severe consequences regarding the parents emotional, mental, and financial status, as well as the consequence of the child dying in utero. Also, the negative consequences regarding the potential inability of parents to accept their childs natural flaws and the potential that parents may set high achievement standards for the genetically selected child appear to be a grave, negative emotional and mental obstacle for the child selected for the rare homozygous HMGA2 allele expression. Finally, the

consideration of negative effects associated with late-onset mental illnesses such as Alzheimers disease and Schizophrenia pose the greatest harm to the most individuals as a whole, such as the parents, wives, husbands, children, grandchildren, friends, and many more. Therefore, Utilitarianism does not deem the use of PGD for non-medically related genes to be ethically or morally responsible for mere desired trait selection. Ronald Green states, Babies by design are in our future, but considering similar scenarios regarding the use of PGD for the selection of non-medically related traits, especially those traits such as the HMGA2 gene, PGD cannot be regarded ethically permissible.

Works Cited Abarado, A.-M. (2009). Designer Babies: Creating Perfection or Breeding Trouble. 1-4. ABC Science. (2012, April 16). Tiny Gene Change Affects Brain Size, IQ. News in Science, 1-2. Agar, N. (2006, January 1). Designer Babies: Ethical Considerations. Retrieved September 27, 2012, from Chang, L.-J., Chen, S.-U., Tsai, Y.-Y., Hung, C.-C., Fang, M.-Y., Su, Y.-N., et al. (2011, September 1). An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening. Retrieved November 28, 2012, from CERM: Davicioni, E., Anderson, M., Finckenstein, F., Lynch, J., Qualman, S., Shimada, H., et al. (2009, February 1). Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group. Retrieved November 28, 2012, from Davis, D. S. (2009, April). The Parental Investment Factor and the Child's Right to an Open Future. Hastings Center Report, 39(2), 24-27. Duel, D. (2012, April 17). Intelligence gene discovered. Retrieved November 28, 2012, from Green, R. M. (2007). Babies by Design: The Ethics of Genectic Choice. Birmingham, New York: HarperCollins. Kai-Yin Chau, 1. G.-W.-C. (2003, May 9). Derepression of HMGA2 Gene Expression in Retinoblastoma Is Associated with Cell Proliferation. Molecular Medicine, 154-165. Robertson, J. A. (2002, October 28). Extending Preimplantation Genetic Diagnosis: Medical and NonMedical Uses. Journal of Medical Ethics, 29(4), 213-216. ScienceDaily. (2012, April 15). New Genes Linked to Brain Size, Intelligence. Retrieved October 26, 2012, from Science News: von Hinke Kessler Scholder, S., Smith, G. D., Lawlor, D. A., Propper, C., & Windmeijer, F. (2010). Child Height, Health and Human Capital: Evidence using Genetic Markers. THE CENTRE FOR MARKET AND PUBLIC ORGANISATION, 1-42. Wilton, L., Thornhill, A., Traeger-Synodinos, J., Sermon, K., & Harper, J. (2008, November 11). The causes of misdiagnosis and adverse outcomes in PGD. Retrieved November 28, 2012, from Human Reproduction: Oxford Journals: