By Jessie Levin (PO’ 18)
Introduction:
Imagine a world where illnesses do not exist and where parents can dictate the specific traits that they want for their future children. Although this world seems like it is thousands of years away, the technology to bring this to fruition is here. If a parent wanted to design a baby with perfect teeth, green eyes, and resistance to dementia, they could. While gene editing technologies have been developed, the laws surrounding their use are outdated. This paper will first introduce gene editing technologies and the current laws around their use. It will then address the ethical implications of germline (egg or sperm) gene editing technologies and provide a hypothetical framework for which this gene editing. This framework, which is based on the decisions that parents already make, can be applied to prevent harm and better the population’s wellbeing.
Part 1: What is CRISPR?
In short, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9) is a novel way of altering an organism’s DNA and therefore altering its makeup. CRISPR works by searching for a genetic sequence of interest. Prior research has mapped many diseases to specific gene sequences.[1] Once this sequence is located, the Cas9 enzyme acts as a pair of scissors to cut out the genetic sequence of interest. After this, the DNA sequence will make repair itself with a new genetic sequence. In this way, researchers can basically copy and paste whatever they want into any DNA segment within the genome.[2] Because we have the capability to essentially ‘copy and paste’ genes of interest into DNA sequences, we can theoretically design humans, be it aesthetically or from health motives.
Part 2: Promising Applications of CRISPR
Currently, CRISPR is being researched for the treatment and prevention of human diseases, although this research is being conducted in cells and animals due to the uncertain risk to human health. CRISPR technology appears to be promising to address both single-gene disorders (e.g. hemophilia) and more complex illnesses (e.g. cancer and HIV).[3]
There are two types of cells: somatic cells and germ cells. Germ cells are egg or sperm and somatic cells are everything else. While gene editing on somatic cells will only affect the specific person, if these gene editing changes were made in germ cells, then they would affect the embryo and the resulting person’s future generations. While someone could alter their germ cells to remove the BRAC2 (breast cancer) gene, they could also alter their germ cells to make their children taller, smarter, or faster. CRISPR and other gene editing technologies can result in fewer illnesses and when applied to germ cells, can prevent certain illnesses down the line. So, gene editing can improve health. Studies have shown that increased health leads to more productive workers.[4] So, as the health of society improves with CRISPR technologies, the population can become more productive.
Part 3: Current Gene Editing Laws
Currently, in the United States, gene editing laws and regulations vary in stringency depending on the situation. While current legislation is relaxed for animals and plants, gene editing laws for humans are under more scrutiny. The FDA regulations concerning the editing of somatic cells came from the Recombinant DNA Advisory Committee.[5] Gene editing is treated and regulated as a biological drug or device. This means that doctors can order gene editing therapy to treat a current disease caused by a single gene mutation such as sickle cell where the therapy only affects the patient.[6] In this case, while the products are heavily regulated, after they enter the market, there is little control over their use.
In the United States, gene editing in embryos or germline cells are heavily restricted. Up until recently, clinical trials which edited the genes of human embryos were banned.[7] In 2017, the US National Academy of Sciences (NAS) Committee put out a report which said that a clinical trial in which human embryos are edited to prevent diseases “ ‘might be permitted, but only following much more research” on the risks and benefits, and “only for compelling reasons and under strict oversight.’”[8] Even though these laws are restrictive now, this report has been seen as a ‘green light’ towards this research. A lab in MIT in 2017 has taken this ‘green light’ and attempted to genetically alter human embryos.[9]
These regulations are restrictive for a good reason. If a mistake occurs as a result of an oversight that could have been regulated, then the future of gene editing for both somatic and germline cells will be pushed back or even outlawed. To have responsible implementation of this technology, the laws need to change only after careful considerations.
Part 4: Ethical Implications of CRISPER
Although somatic and germline editing have ethical implications, this paper will focus on the moral questions surrounding germline uses of CRISPR because of its potential for generational change. Many ethical questions arise. First off, if we do allow these edits, what types of changes should be allowed? Does preventing cancer produce the same level of ‘good’ as preventing dwarfism? What about cancer compared to changing a child’s eye color?
Thinking practically, who should have access to this technology? How would we get consent of the embryo for these changes? By using CRISPR on certain diseases, are we telling those afflicted by these diseases that they are not worthy in our society? Additionally, if we were design the next generation of humans, would be the guiding principles? Would we want to design humans to be the best athletes, insanely smart, or, would we have an artificial genetic diversity? Should we ‘play God’?
Many compare modern gene editing with the eugenics movement of that spawned from social Darwinism. In the United States, the eugenics movement was used as a way of controlling the number of undesirable people (e.g. poor people, immigrants, people of color, mentally ill populations) through sterilization programs in the 1900s.[10] While this program’s legality was questioned in Buck v. Bell (1927), it was upheld by the Supreme Court. Justice Wendell Holmes, in his opinion stated that “It is better for all the world, if instead of waiting to execute degenerate offspring for crime, or to let them starve for imbecility, society can prevent those who are manifestly unfit from continuing their kind….Three generations of imbeciles is enough”.[11] Although the eugenics movement lost a lot of steam after the atrocities of Nazi Germany, forced sterilization was still practiced in some states up until the 1970s.[12], [13]
Out of the many ethical implications presented, this paper will attempt to address the following: access inequality, the types of diseases CRISPR should work on (and the implications for the disability community) and the consent of the fetus. These, along with many other ethical issues not presented in this paper will need to be addressed before CRISPR can move towards clinical applications.[14]
Part 5: A Hypothetical Framework to Implement CRISPER Technology
Currently, embryo gene editing in the United States is not supported by federal funding.[15] However, that does not stop private funders from supporting this type of research. As it stands, in the U.S., germline gene editing is legal for research purposes and the embryos never have a chance to reach life.[16] This is not the case in Canada, where researchers can land in jail for genetically modifying embryos, even if these embryos will never reach life.[17] Because recent research has shown that it is possible to modify the embryos, there should be more work changing the laws to represent the reality of the science we now have.[18]
One way to update the laws would be to allow CRISPR for embryo gene editing, but only to prevent or correct health conditions with long-term detrimental effects in line with recent NAS recommendations. While ‘long-term detrimental effects’ needs more research to be better defined, for this rough framework, we can draw the line at around 35 Quality Adjusted Life Years (QALYs), which is about half of the current life expectancy of the United States.[19] This framework allows for the laws to get up to speed with current technological advances while also taking into consideration the sociological fears of sterilizing ‘undesirable’ people that was first brought up with the eugenics movement. This framework still allows some aspect of reproductive choice and the rationale for this framework is health, instead of race-based sterilization.
Part 6: In Support of this Framework
The basis of this framework is to better the health of our society. If we have the tools to prevent harm and still allow it, is that moral? Why should we allow babies to be born with debilitating diseases and live their lives in pain? Julian Savulescu and Guy Kahane approach this question in their 2009 article titled “The Moral Obligation to Create Children with the Best Chance of the Best Life”. They introduce the principle of procreative benefice, the idea that parents have a “significant moral reason to select the child…whose life can be expected, in light of the relevant available information, to go best or at least not worse than any of the others.”[20] They argue that parents already try to give their prospective children the best life by waiting until the time is ‘right’ (environmentally, finically, emotionally, ect.) to conceive and that these parents would be seen as responsible even though they would be bringing about a different child than if they had conceived at the present moment.[21] They then pose that selecting for advantages is no different than not selecting for disadvantages. [22] So, by giving parents the option to use CRISPR technologies, they will be better able to practice the principle of procreative benefice.
Additionally, how is this different from what we do normally? Pheromones are chemical messengers that, according to a 1995 study by Claus Wedekind et al., can alert a potential mates to the composition of your immune system as a result of one’s MHC genes. In this study, he gave men t-shirts to wear over the span of two days. Once the time was up, women smelled the shirts and sorted them in terms of intensity, pleasantness, and sexiness. Interestingly, women were more attracted to the shirts that were worn by men with different MHC gene compositions.[23] When different MHC genes intersect, it results in a child with a healthier immune system.[24] This proposed CRISPR framework is an extension of the actions that we humans already to give our future children the best health possible.
Part 7: Response to Criticism
Disability advocates say that being differently abled enriches society when it comes to diversity.[25] Furthermore, by making the decision before the baby is born, the individual does now have a choice in how their disability is changed. While they are correct that the individual’s choice is diminished, in some states, it is legal to abort a fetus after learning the results of prenatal testing.[26] In this case, the choices are being made regarding genetics as would have been made with this proposed CRISPR framework.
Furthermore, by allowing this CRISPR framework, it can be argued that the abortions after prenatal testing allows more general harm to both the fetus and the mother. Additionally, as society progresses towards increased inclusivity towards differently abled individuals and certain treatments improve, we can reevaluate the cut off point for CRISPR. Because in some states we already allow for abortions after these procedures, the proposed CRISPR framework is more humane.
Another criticism against this technology would be its availability and access. If it was able to get rolled out, who would be able to afford the cost? While it is not certain how much this procedure would cost, it would definitely be in the tens of thousands of dollars. For reference, Harvard University charges non-profit institutions over $19,000 to perform a CRISPER gene fix on one gene.[27]
Should we have the State pay for this to promote equity or should we fold it into the already complex U.S. health insurance system? If cost or access is a barrier, then are we basically allocating better health outcomes to those who can access and afford it. Some health insurance companies, such as Vantage Blue from Blue Cross Blue Shield of Rhode Island, have already issued policies where they do not include gene therapy in their coverage.[28] If they will not cover gene therapy for somatic cells, it is safe to assume that they will not cover CRISPR technologies for embryos. To address this access and equity concern, CRISPR can be made publically available. It could be funded by some tax or initiative. Part of this funding could also going towards ensuring successful implementation and making sure that everyone who wants this is able to get it. While some might not agree with this proposed egalitarian approach, it provides the best way to mitigate inequality concerns.
Part 8: Conclusion and Final Thoughts
Although the technology is now possible for germline editing, the laws to regulate this process are outdated and restrictive. While the proposed framework is not perfect, it does provide a helpful place to start thinking about this technology’s possible implementation into society. By allowing the use of CISPR technologies to prevent or mitigate the consequences of conditions with conditions with long-term health effects, we can reduce the level of harm in our society while being culturally sensitive. The next step forward would be to determine which particular long-term conditions should CRISPR be applied to. While this paper assumed that conditions which cost 35 QALYs (around half of the U.S. life expectancy) should be allowed to have CRISPR, this fails to take into account the feasibility aspect of implementing CRISPR. It might be too resource intensive to allow CRISPR for all of these diseases so further work needs to define this cut-off point.
[1]” Initial sequencing and analysis of the human genome.” Nature412, no. 6846 (2001): 565-66. doi:10.1038/35087627.
[2] “What are genome editing and CRISPR-Cas9? – Genetics Home Reference.” U.S. National Library of Medicine. Accessed March 11, 2018. https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting.
[3] Ibid.
[4] “Exploring the Value Proposition for Workforce Health: Business Leader Attitudes about the Role of Health as a Driver of Productivity and Performance.” February 2015. https://www.shrm.org/ResourcesAndTools/hr-topics/benefits/Documents/HPP-Business-Leader-Survey-Full-Report_FINAL.pdf.
[5] Charo, R. Alta. “The Legal and Regulatory Context for Human Gene Editing.” Issues in Science and Technology. Accessed April 14, 2018. http://issues.org/32-3/the-legal-and-regulatory-context-for-human-gene-editing/.
[6] Ibid.
[7]Regalado, Antonio. “U.S. Panel Endorses Babies Gene-edited with CRISPR.” MIT Technology Review. February 14, 2017. Accessed April 13, 2018. https://www.technologyreview.com/s/603633/us-panel-endorses-designer-babies-to-avoid-serious-disease/.
[8] Reuters. “U.S. Scientists Urge ‘Serious Consideration’ Of Gene Editing In Human Embryos.” The Huffington Post. February 15, 2017. Accessed April 14, 2018. https://www.huffingtonpost.com/entry/us-scientists-urge-serious-consideration-of-gene-editing-in-human-embryos_us_58a48664e4b03df370dc6fcf.
[9] Connor, Steve. “First Human Embryos Edited in U.S., Using CRISPR.” MIT Technology Review. December 29, 2017. Accessed April 14, 2018. https://www.technologyreview.com/s/608350/first-human-embryos-edited-in-us/.
[10]Ko, Lisa. “Unwanted Sterilization and Eugenics Programs in the United States.” PBS. January 26, 2016. Accessed March 13, 2018. http://www.pbs.org/independentlens/blog/unwanted-sterilization-and-eugenics-programs-in-the-united-states/
[11] Ibid.
[12]Bouche, Teryn, and Laura Rivard. Nature News. September 18, 2014. Accessed March 13, 2018. https://www.nature.com/scitable/forums/genetics-generation/america-s-hidden-history-the-eugenics-movement-123919444.
[13] Ko, Lisa. “Unwanted Sterilization and Eugenics Programs in the United States.” PBS. January 26, 2016. Accessed March 13, 2018. http://www.pbs.org/independentlens/blog/unwanted-sterilization-and-eugenics-programs-in-the-united-states/
[14] Reardon, Sara. “Global summit reveals divergent views on human gene editing.” Nature News. December 08, 2015. Accessed March 13, 2018. https://www.nature.com/news/global-summit-reveals-divergent-views-on-human-gene-editing-1.18971.
[15] Brown, Kristen V. “This Outdated Law Makes CRISPR Illegal in Canada-and That’s Hurting Science.” Gizmodo. November 20, 2017. Accessed March 13, 2018. https://gizmodo.com/this-outdated-law-makes-crispr-illegal-in-canada-and-th-1820612582.
[16] Ibid.
[17] Ibid.
[18] Connor, Steve. “First human embryos edited in U.S., using CRISPR.” MIT Technology Review. December 29, 2017. Accessed March 13, 2018. https://www.technologyreview.com/s/608350/first-human-embryos-edited-in-us/?set=608342.
[19] “National Center for Health Statistics.” Centers for Disease Control and Prevention. December 21, 2017. Accessed March 11, 2018. https://www.cdc.gov/nchs/products/databriefs/db293.htm.
[20] Savulescu, Julian, and Guy Kahane. “The Moral Obligation To Create Children With The Best Chance Of The Best Life.” Bioethics 23, no. 5 (2009): 274-90. doi:10.1111/j.1467-8519.2008.00687.x.
[21] Ibid.
[22] Ibid.
[23] Wedekind, Claus, Thomas Seebeck, Florence Bettens, and Alexander J. Paepke. “MHC-Dependent Mate Preferences in Humans .” Biological Sciences 260, no. 1359 (June 22, 1995): 245-49. doi:10.1098/rspb.1995.0087.
[24] Ibid.
[25] Linton, Simi, Susan Mello, and John O’Neill. “Disability Studies: Expanding the Parameters of Diversity.” The Radical Teacher 47 (Fall 1995): 4-10. http://www.jstor.org/stable/20709848.
[26] Marco, Tony. “New Ohio law prevents abortions in Down syndrome cases.” CNN. December 22, 2017. Accessed March 13, 2018. https://edition.cnn.com/2017/12/22/health/ohio-governor-signs-down-syndrome-abortion-ban/index.html.
[27] “Genome Editing Services.” HSCI iPS Core Facility. Accessed March 13, 2018. https://ipscore.hsci.harvard.edu/genome-editing-services.
[28] “Who will pay for CRISPR?” STAT. June 23, 2017. Accessed March 11, 2018. https://www.statnews.com/2017/06/26/crispr-insurance-companies-pay/.
