The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination of the Disabled: Analysis of Mitigating Factors

The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination of the Disabled: Analysis of Mitigating Factors Blaine T. Bettinger, Ph.D., J.D. April 2009 I. Introduction Preimplantation Genetic Diagnosis (“PGD”) is a technique used to characterize genetic traits and chromosomal structure of embryos that are created through in vitro fertilization (“IVF”).1 During a traditional IVF cycle, eggs are harvested from a woman following ovarian stimulation and are fertilized with sperm to create embryos.2 Two to four days after fertilization, one or two cells are removed from the eight-celled embryos for genetic analysis.3 Following the analysis, the selected embryo or embryos are implanted in the woman’s uterus. To characterize genetic traits or chromosomal structure, the DNA of the harvested embryonic cells is isolated and subjected to either polymerase chain reaction (PCR) analysis to examine specific genetic sequences (such as those associated with cystic fibrosis, sickle cell anemia, and Huntington disease) or fluorescent in-situ hybridization (FISH) to examine conditions such as chromosomal abnormalities.4 Currently, PGD analysis is typically limited to suspected traits or conditions based on the genotypes or family history of the biological parents. 5 1 Molina B Dayal & Shvetha M Zarek, Preimplantation Genetic Diagnosis, EMEDICINE, http://emedicine.medscape.com/article/273415-overview (last visited Mar. 25, 2009). 2 Id. 3 Id. 4 Id. 5 Id.

However, as new technology such as microarray analysis becomes affordable, a PGD test will include thousands of genetic traits and reveal a wealth of information about the genetic profile of the embryo.6 As a result, parents will have the ability to screen embryos based on thousands of tested traits. The ability of parents to screen tested embryos has raised concerns, even at the current technological state of PGD testing, about the potential for increased discrimination against individuals possessing or exhibiting genetic disabilities.7 These concerns are based upon the belief that as society is given the tools to select against specific genetic traits, people who possess those traits will be stigmatized and marginalized, leading to increased discrimination. Timothy Krahn of Novel Tech Ethics summarized the argument thusly: “The moral danger does not lie with the people who seek [PGD] testing; rather, the danger lies in how this testing could promote further stigmatization of and discrimination against people with genetic impairments or their parents. Indeed, testing could entrench a culture of prevention and perfectionism and promote a culture of intolerance.”8 Even the Pope has decreed that using PGD to screen embryos based on genetic disorders is discrimination.9 6 See, e.g. Justin Perrone, Empire Genomics Will Provide Reprogenetics With Chips for IVF Cell Screening Worldwide, BIOARRAY NEWS, Oct. 16, 2007, http://www.genomeweb.com/arrays/empire-genomics-will-provide- reprogenetics-chips-ivf-cell-screening-worldwide (last visited Mar. 25, 2009) (discussing the recent success of microarray chip analysis of the genomic profile of single cells). 7 See, e.g., Jaime King, Predicting Probability: Regulating the Future of Preimplantation Genetic Screening, 8 YALE J. HEALTH POL'Y, L. & ETHICS 283 (2008) (arguing that “widespread use of the technique can harm not only the individuals involved in it, but also society in general by increasing discrimination, stigmatization, and health disparities.”); J.C. Roberts, Customizing Conception: A Survey Of Pre-implantation Genetic Diagnosis And The Resulting Social, Ethical, And Legal Dilemmas, 2002 DUKE L. & TECH. REV. 0012 (2002) (noting that “[t]he disability discrimination claim maintains that prenatal or preimplantation screening for disabilities results in discrimination against those with the disability by reducing the numbers of people affected.”); David S. King, Preimplantation Genetic Diagnosis and the ‘‘New’’ Eugenics, 25 J. MED. ETHICS 176 (1999). 8 Timothy Krahn, Where Are We Going With Preimplantation Genetic Diagnosis?, 176 CMAJ 1445, 1445 (2007). 9 Nicole Winfield, Pope Decries Genetic Discrimination, THE SYNDEY MORNING HERALD, Feb. 22, 2009, http://news.smh.com.au/breaking-news-world/pope-decries-genetic-discrimination-20090222-8edd.html. 2

Just as troubling, widespread adoption of PGD technology could ultimately lead to discrimination along socioeconomic lines. Depending on the cost of PGD and IVF cycles, socioeconomic classes unable to afford those costs will be unable to select against certain genetic traits. As a result, the conditions associated with those genetic traits will manifest in an increasingly smaller percentage of higher socioeconomic classes, in effect making the manifest condition (which will usually be called a disability) one that belongs primarily to lower economic classes. The argument that selection against specific genetic traits will lead to increased discrimination is both compelling and troubling. Indeed, it is reasonable to conclude that if a large number of people use PGD to select against traits they consider to be disabilities then the probability of increased discrimination and marginalization would be greatly increased. However, as this Note argues, most participants in the PGD disability debate overlook important limitations of both trait selection and large-scale PGD adoption that will likely mitigate the negative potentially negative impact of PGD technology. II. Trait Selection Limitations Will Mitigate Discrimination Resulting From PGD In a recent study of assisted reproductive technology clinics throughout the United States, researchers collected data from more than 3,000 PGD cycles.10 According to the analysis, 75% of the examined PGD cycles were for detection of chromosomal abnormalities (including aneuploidy and rearrangements), 15% were for detection of X-linked disorders (e.g., Duchenne muscular dystrophy) and autosomal disorders (e.g., Huntington’s disease, hereditary breast 10 Susannah Baruch, David Kaufman, & Kathy L. Hudson, Genetic Testing of Embryos: Practices and Perspectives of U.S. In Vitro Fertilization Clinics, 89 FERTILITY AND STERILITY 1053 (2008). 3

cancer, and Alzheimer disease), and 9% were for sex selection.11 The remaining 1% were for HLA typing.12 The study thus suggests that currently, approximately 90% of PGD cycles are used to screen for serious medically-relevant genetic disorders. As PGD embraces the rapidly advancing knowledge of the genetics underlying non- medical traits such as eye color, height, or minor medical traits such as anti-arteriosclerosis propensity, for example, embryo selection will potentially include a number of these traits. As is discussed below, this increase in information will likely have a strong mitigating impact on the potential for PGD-induced disability discrimination. Figure 1 is a chart showing the cross of two individuals who are the biological parents of a group of embryos. Each parent in the cross possesses the autosomal-dominant mutation that causes Huntington’s Disease (black circle), and each possesses one gene involved in a cooperative mechanism to increase lifetime resistance to arteriosclerosis (red or green circle); offspring must possess both cooperative genes to effectively possess the resistance. As the chart shows, if the embryo selection is based on PGD analysis of just the autosomal-dominant mutation for Huntington’s Disease, then 4:16 (or 25%) of embryos on average will not inherit the mutation from either parent. However, if the embryo selection is based on both the absence of the autosomal-dominant mutation and the presence of the two cooperative alleles, then just 1:16 (or 6.25%) of embryos on average will satisfy those criteria (boxed in yellow). With every new trait that is added to the selection criteria, the possibility of obtaining the desired outcome is significantly lowered. Indeed, rather than this simple cross, a diagram that examines the inheritance of 5, 10, or 50 potentially serious genetic disorders from two biological parents would be incredibly complex, 11 Id. 12 Id. 4

and the chances of obtaining a “perfect” embryo that satisfies all criteria are vanishingly small. Screening for this many serious genetic disorders is not as unlikely as it may seem, considering recent suggestions that every human being harbors a genetic propensity for between 5 and 50 disorders.13 13 This statement is generally attributed to Francis Collins, M.D., Ph.D., former director of the National Human Genome Research Institute. See, e.g., Press Release, Rep. Slaughter, Author of Genetic Information Nondiscrimination Act, Applauds Bill’s Passage in House of Representatives, May 1, 2008, http://www.louise.house.gov/index.php?option=com_content&task=view&id=964&Itemid=1 (“each one of us is estimated to be genetically predisposed to between 5 and 50 serious disorders.”); Roseann Gumina, The Human Genome Project and the Next Medical Revolution, MEDSCAPE TODAY, 1998, http://www.medscape.com/viewarticle/431916 (citing Dr. Collins for the proposition that “each human being has 5 to 50 genetic flaws.”); Nicholas Wade, Gene Mutation Tied to Colon Cancers in Ashkenazi Jews, N.Y. TIMES, Aug. 26, 1997 (quoting Dr. Collins directly as saying that “[w]e are all flawed, we all carry 5 to 50 serious genetic misspellings.”). 5

Figure 1. Representation of a Three-Trait Cross14 14 The first allele (black circle) is an autosomal-dominant genetic disorder. The second allele (red circle) and third allele (green circle) represent a cooperative multiallelic genetic trait; in this example, two genes are working together to cause a particular phenotype. If embryo selection is based on analysis of just the autosomal-dominant allele, 4:16 (25%) of embryos on average will be suitable for implantation. If the embryo selection is based on the absence of the autosomal-dominant allele and the presence of both cooperative multiallelic genes, then just 1:16 (6.25%) of embryos on average will be suitable for implantation (boxed in yellow). This figure is adapted from Figure VIII.c in German National Ethics Council, Genetic Diagnosis Before and During Pregnancy: Opinion 162- 63 (2003), available at www.ethikrat.org/_english/press/Opinion_Genetic_Diagnosis.pdf. 6

The problem of multiple trait selection is further complicated by the relatively high rate of chromosomal abnormalities in IVF embryos. A 2003 study suggested that – in high-risk groups, at least – as many as 68% of embryos possess chromosomal abnormalities.15 Thus, even if these embryos possess no allelic disorders, the chromosomal abnormalities render them unfit for implantation. The opportunity for selection is further reduced by the simple fact that most fertility centers only harvest an average of 6 to 15 eggs for in vitro fertilization.16 It is logical to assume that in a complex screen that tests thousands of genetic traits, the limited number of selections based on random assortment and the limited number of embryos created will most likely result in the most serious traits being selected against rather than the most desirable traits being selected for; the majority of parents are undoubtedly more likely to choose against serious genetic disorders regardless of the presence or absence of desirable non- medical traits than to choose for favorable non-medical traits despite the presence of a serious genetic disorder. However, less threatening genetic disorders – which themselves are termed disabilities under the current broad definition – will be less likely to be selected against because there are so many to choose from and only a limited number of embryos with which to make the choice; it is slightly more likely that in this situation parents will select desirable non-medical traits over less threatening genetic disorders. Thus, the negative discriminatory impact of PGD will likely be limited to the most serious life-threatening genetic diseases simply because those are the ones most likely to be consistently selected against. 15 Lawrence Werlin, et al., Preimplantation Genetic Diagnosis as Both a Therapeutic and Diagnostic Tool in Assisted Reproductive Technology, 80 FERTILITY AND STERILITY 467 (2003). 16 Fertility Specialists of Dallas, In Vitro Fertilization Overview, http://www.fertilitydallas.com/IVF_fertility_dallas_IVF_overview.html (last visited Mar. 26, 2009) (“[t]he average number of eggs retrieved at IVF is between 8 and 15.”); G. David Adamson, The Stumbling Blocks to IVF, http://www.medicinenet.com/script/main/art.asp?articlekey=54431 (last visited Mar. 26, 2009) (“[t]he average number of eggs retrieved is about 10 to 12 eggs for each retrieval.”); Advanced Fertility Center of Chicago, IVF overview and general information about the in vitro fertilization process and procedures, http://www.advancedfertility.com/ivf.htm (last visited Mar. 26, 2009) (ranging from 6.8 to 10.3 eggs per retrieval). 7

Limiting negative selection – and therefore potential discrimination – to the most serious genetic disorders is arguably little comfort to those who suffer from those disorders or indeed anyone concerned about the potential for discrimination. However, understanding this limitation to PGD selection will allow government agencies and society at large to focus anti- discrimination efforts on those limited most likely to suffer the potential discriminatory impact of PGD. III. The Limited Use of PGD Will Mitigate Potential Discriminatory Effects In 1990, for the first time, a child was born from an embryo subjected to PGD.17 As a result of the preimplantation screening, the girl was born free of the ΔF508 deletion associated with cystic fibrosis.18 Just 16 years later in 2006, 4-6% of the 138,000 IVF cycles in the United States – roughly 7,000 cycles – included PGD.19 Although these figures represent a rapid rise in the frequency of PGD since its first use, PGD is currently used in only about 0.1% of all pregnancies in the United States.20 The low frequency of PGD testing associated with IVF cycles has significant ramifications on the ability of PGD to affect discrimination against the disabled. If concerns about increased discrimination due to PGD are based on either (i) a lower overall frequency of a genetic disorder in the human population (or some subpopulation) due to selection against that 17 A.H. Handyside, et al., Birth of a Normal Girl After In Vitro Fertilization and Preimplantation Diagnostic Testing for Cystic Fibrosis, 237 NEJM 905, 905 (1992). 18 Id. 19 See, e.g., Baruch et al., supra note 10 (4-6% of IVF cycles); CDC, Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports, http://www.cdc.gov/ART/ART2006 (last visited Mar. 26, 2009) (138,198 ART cycles in 2006). 20 American Pregnancy Association, Pregnancy Statistics, http://www.americanpregnancy.org/main/statistics.html (last visited Mar. 26, 2009) (approximately 6,000,000 pregnancies per year). 8

disorder by PGD; or (ii) on society’s adoption of a “culture of prevention and perfectionism”21 (that is, that people with the most serious genetic disorders are unfit or inferior),22 then arguably there must first be widespread adoption of the technology. On the other hand, if PGD is only routinely used by a limited number of individuals – such as those facing fertility problems or life-threatening inheritable diseases, for example – it is much more difficult to support the argument that PGD could result in disability discrimination; there would arguably not be enough of an impact on either disability frequencies or societal/cultural views to promote discrimination. A. Parents Who Reject PGD Testing A primary limitation on the widespread adoption of PGD (and therefore on the ability of PGD to negatively affect discrimination against the disabled) is the acceptance of the technology. To “promote further stigmatization of and discrimination against people with genetic impairments,”23 PGD must be widely accepted; if society rejects either PGD as a whole or rejects specific uses of the technology, the ability of PGD to influence stigmatization or discrimination will be severely limited. Arguably, widespread rejection of PGD or specific uses thereof could actually result in the opposite effect; there could be increased support for and awareness of the disabled because of widespred disfavor with the technology. In 2006, the Genetics and Public Policy Center (“GPPC”) at The Johns Hopkins University published one of the largest analyses of public opinion regarding PGD.24 Based on surveys and/or interviews with over 6,000 people, the results suggest that 42% of Americans 21 Krahn, supra note 8 at 1445. 22 The President’s Council on Bioethics, Beyond Therapy: Biotechnology and the Pursuit of Happiness, October 2003, http://www.bioethics.gov/reports/beyondtherapy/ (last visited Mar. 26, 2009). 23 Krahn, supra note 8 at 1445. 24 Kathy L. Hudson, Preimplantation Genetic Diagnosis: Public Policy and Public Attitudes, 85 FERTILITY & STERILITY 1638 (2006). 9

disapprove of using PGD to select against adulthood diseases such as cancer, and 32% of Americans do not approve of using PGD even to prevent fatal childhood disease.25 Additionally, fully 72% of Americans disapprove of using PGD to select embryos based on non-health characteristics (such as intelligence, height, etc.).26 The survey provides evidence that a significant percentage of individuals in the United States disapprove of using PGD for any use, while still a larger percent do not approve of using PGD to select for or against less serious traits (such as adulthood diseases, behavior, and appearance). The anti-PGD views of millions of adults will significantly limit the widespread adoption of the technology and any resultant negative impact on discrimination against the disabled. B. Unintended Pregnancies There are number of factors that may significantly limit widespread adoption of PGD and thus potentially mitigate the impact of PGD on discrimination of the disabled. One example of a potentially mitigating factor is the number of unintended pregnancies in the United States. Unintended pregnancies can be the result of such things as lack of contraception, contraceptive failure or misuse, or involuntary sex. Since unintended pregnancies are by definition unplanned, they are completely in vivo and thus there is no opportunity for PGD testing. Unintended pregnancies represent a significant percentage of all pregnancies in the United States.27 In 1994, there were approximately 3.95 million births and 1.43 million 25 Id. 26 Id. 27 Stanley K. Henshaw, Unintended Pregnancies in the United States, 30 Family Planning Perspectives 24, 26 (1998) available at http://www.guttmacher.org/pubs/journals/3002498.html (this data does not include miscarriages). 10

abortions, totaling 5.38 million pregnancies.28 Of those 5.38 million pregnancies, 3.1 million – a full 49% – were unintended, a number that is still largely accurate today.29 Of these unintended pregnancies, a total of 46% ended in births and 54% ended in abortion.30 The fact that 23% of all children – approximately 1.24 million – born in 1994 were not planned and thus could not have undergone PGD testing has a potentially significant impact on the concern that PGD will increase discrimination against the disabled. First, the number of unintended pregnancies suggests that if PGD were in fact to become much more common (and thus more likely to impact discrimination), the concern about lower frequencies of children born with genetic disabilities will be significantly reduced by the 50% of pregnancies (and resulting children) who cannot undergo PGD testing. If, as this Note argues, the ability of PGD to impact disability discrimination hinges on widespread adoption of PGD and potentially on lower frequencies of children born with genetic disabilities, then unintended pregnancies will likely undermine both and thus mitigate the negative impact of PGD on discrimination against the disabled. C. Other Aspects of Unintended Pregnancies Unintended pregnancies might, however, affect discrimination against the disabled in other ways if PGD testing becomes routine. Although unintended pregnancies will tend to mitigate overall adoption of PGD, these pregnancies might result in disabilities and any resulting discrimination being concentrated in lower socioeconomic ranks. At its extreme, this may result 28 Id. 29 James Trussell and L.L. Wynn, Reducing Unintended Pregnancy in the United States, 77 Contraception 1 (2008), available at http://www.arhp.org/uploadDocs/journaleditorialjan2008.pdf. 30 Henshaw, supra note 28 at 26. 11

in a “social underclass”31 that is stigmatized and discriminated against because they did not undergo PGD as part of their pregnancy. In 1994, the rate of unintended pregnancies was “highest among women who were aged 18-24, unmarried, low-income, black or Hispanic.”32 Indeed, 25% of all unintended pregnancies in 1994 occurred below the poverty level (which was then $17,020 for a family of four33), and another 25% unintended pregnancies occurred in the income bracket between the poverty level and twice the poverty level.34 Thus, PGD and unintended pregnancies have the potential to concentrate disabilities and discrimination against the disabled in lower socioeconomic ranks if: (i) PGD is so widely adopted that it places a societal pressure on parents to undergo PGD testing; and (ii) the disparate frequency of unintended pregnancies continues to follow historical values (i.e. a higher percentage of unintended pregnancies occur in lower socioeconomic ranks). Given the incredibly slow adoption of PGD to date, it is far from clear that it has or will have the societal support needed to impact disability discrimination. Alternatively, although unintended pregnancies are likely to mitigate the potential impact of PGD on disability discrimination, large-scale adoption of PGD testing might in turn have an impact on the outcome of unintended pregnancies. For example, if society embraces large-scale PGD testing, there might be increased motivation for parents of an unintended pregnancy to terminate that pregnancy and thus avoid the risk of disabling genetic disorders. While this Note has examined PGD separate from the many issues associated with prenatal testing, it is possible 31 Rebecca E. Kopp, Preimplantation Genetic Diagnosis, http://www.ndsu.nodak.edu/instruct/mcclean/plsc431/students/koop.htm (last visited Apr. 10, 2009). 32 Trussell and Wynn, supra note 29 at 1. 33 Id. 34 Id. 12

that there will be increased societal pressure for an individual facing an unintended pregnancy to undergo prenatal testing as the result of the cultural approval and adoption of PGD. If the inability to undergo PGD because of an unintended pregnancy ultimately leads to increased abortion of fetuses with a disability, there is the potential that this increase will promote discrimination against those who have or are born with those disabilities. Again, however, this would require that: (i) PGD is so widely adopted that it is able to place this type of societal pressure on the parents of unintended pregnancies; and (ii) a significant proportion of parents of unintended pregnancies decide to terminate pregnancies involving disabilities. It remains unclear that PGD will be so significantly widespread as to possess the degree of societal pressure required under the current analysis. D. Parents Who Are Unable to Afford PGD Testing In addition to adults who might reject the use of PGD for personal, religious, or other similar reasons, there are potential biological parents who do not or would not use PGD simply because the technology is too expensive. Although there is no official data regarding the average cost of PGD in the United States, most sources suggest that the cost ranges from $3,000 to $5,000 per PGD cycle.35 This cost is in addition to the costs already associated with IVF. Additionally, while IVF cycles might be covered by health insurance, it is less clear that PGD 35 Barbara Collura, The Costs of Infertility Treatment, Resolve: The National Infertility Association, available at http://www.resolve.org/site/PageServer?pagename=lrn_mta_cost (average cost of PGD is $3,550); Fertility ProRegistry, PGD Sex Selection, http://www.fertilityproregistry.com/content/pgd_sex_selection.asp (last visited Apr. 15, 2009) (“[t]he cost of Preimplantation Diagnosis and Sex Selection range from $3000 to $5000”); Fertile Hope, Genetic or Inheritable Cancers, http://www.fertilehope.org/learn-more/cancer-and-fertility-info/genetic-or- inheritable-cancers.cfm (last visited Apr. 15, 2009) (“[o]n average, the cost of PGD is around $5,000 per cycle.”); Chelsey Langland, Thinking About PGD, StorkNet’s Infertility Cubby, http://www.storknet.com/cubbies/infertility/pgd.htm (last visited Apr. 15, 2009) (“[a]verage costs [of PGD] seem to fall between $2,500 and $5,000.”). 13

will be covered.36 Similar to potential biological parents that refuse to adopt PGD for non- economic reasons, parents who are unable to afford PGD will significantly limit the widespread adoption of the technology and any resulting negative impact on discrimination against the disabled. It is, however, possible that PGD will eventually become so inexpensive that cost is no longer a barrier for individuals, and thus at that point cost will no longer limit the adoption of PGD. Unfortunately, the high cost of PGD could potentially add to the social underclass problem discussed previously. If affluent individuals are more likely to undergo PGD testing than individuals in lower socioeconomic ranks, disabilities and discrimination against the disabled could be concentrated in the social underclass. IV. Conclusion The concern that PGD could promote a culture of perfection and cause the stigmatization of and discrimination against the genetically disabled is a valid and troubling one. In an effort to achieve equality, the disabled have surmounted numerous challenges mounted by both individual biases and technological developments. Widespread adoption of PGD threatens to mount yet another challenge for the disabled. There are, however, a number of factors that will limit the widespread adoption of PGD and the subsequent effects on discrimination against the disabled. Traditional PGD – that is, without any genetic modification of the embryo – is severely limited in its ability to select for more than a few traits; the inheritance of non-linked genetic traits results in genetically complex 36 See, e.g., Randy S. Morris, M.D., PGD – Preimplantation Genetic Diagnosis, http://www.ivf1.com/pgd/ (last visited Apr. 15, 2009) (“[i]t is very unlikely that PGD will be covered by your insurance [since] [m]ost insurance companies still consider PGD to be experimental even though we have been doing PGD for more than ten years.”). 14

embryos that contain a random mixture of traits from both parents. As a result, it is likely that parents will use the limited number of embryos gathered during a IVF/PGD cycle to select against the most serious traits rather than for more benign favorable traits. Additionally, widespread use of PGD is limited by several factors including unintended pregnancies, rejection of the technology for a variety of personal reasons, and cost barriers. Although these factors carry the threat of potentially concentrating disabilities in lower socioeconomic ranks, they will also significantly limit the widespread adoption of PGD technology. Understanding that there are limitations on the adoption of PGD will allow scientists, ethicists, and legislators to commit resources to further study the reasons behind the limitations and promote equitable use of the technology. For legislators, this might include diverting resources to anti-discrimination efforts for those afflictions most likely to be selected against by PGD. Through a more informed analysis of the many factors limiting the adoption of PGD, lawmakers will be more prepared to understand the potential applications of the technology and legislate accordingly. 15

The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination of the Disabled: Analysis of Mitigating Factors

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The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination of the Disabled: Analysis of Mitigating Factors — Document Transcript