Ari Belotserkovsky 1004909067 04-13-2021 Unmasking the Value of Human Embryo Genome Editing Introduction There is persistent effort by the scientific community to advance medicinal biotechnology with the goal of eliminating debilitating hereditary diseases. Despite this effort there are practical and ethical barriers that prevent the acceleration of controversial biotechnology and its application on humans. These barriers include red tape, development of a variety of safety protocols, approval from ethics committees, enduring the many phases of testing, etc. Moreover, hereditary diseases involve genetic predisposition to the disease, so an ideal method of combating these diseases is by eliminating or fixing the defective gene, and moral quandary arises when debating whether such a method is ethically permissible. Nevertheless, we must accept the possibility that at one point in time controversial biotechnology such as human genome modification will be accessible for patients with a hereditary disease. The aim of this research essay is to demonstrate that embryonic genetic modification is ethically permissible, whether to create model organisms or eliminate hereditary disease. This research paper will also examine the case of a scientist known as Dr. He whose experiments resulted in the birth of genetically modified human twins. Additionally, 4 reasons will be provided to rationalize this perspective; (1) our genomes can be influenced by a variety of medicinal products and even our environment, yet such effects are deemed ethically permissible since they have health benefits or are difficult to combat. (2) Embryonic genetic modification has enabled the creation of model organisms for research studying hereditary diseases. Without this technology, researching hereditary disease would be impossible since it involves direct genome alteration to produce the disease. (3) Human embryo genome editing can be effectively utilized to eliminate hereditary diseases, as demonstrated by Dr. He’s experiments. (4) The intention of this technology does not extend to genetic enhancement for desire. Ari Belotserkovsky 1004909067 04-13-2021 The creation of designer babies would loosen the boundary between purposeful genetic modification and desirable genetic modification. The Case of Dr. He’s Experiments & the Birth of Lulu and Nana In China, HIV-positive couples face tremendous difficulty when attempting to conceive a healthy baby (Baylis, 2019). The Chinese government neglects their financial status and society typically gives a strong negative connotation to the term HIV, thereby influencing prejudice and discrimination against HIV-positive couples (Baylis, 2019). Dr. He attempted to alleviate the financial and psychological burdens of raising a baby that is highly susceptible to HIV by curing the inherent defect responsible for this. Unfortunately, the defect is genetic and genome editing is currently not permitted in China (Baylis, 2019). Despite this, Dr. He performed numerous experiments to develop the safest protocol necessary to carry out genome editing of a human embryo to eliminate the defective gene (Baylis, 2019). Dr. He prevailed in his experiments and a HIV-positive couple that volunteered for the experiment successfully managed to carry out the pregnancy term, ultimately giving birth to the first two genetically modified babies named Lulu and Nana (Baylis, 2019). According to Dr. He’s results, only one of the babies is resistant to HIV, but nevertheless, all parties in the experiment were content with the results (Baylis, 2019). This is an important distinction; Dr. He and the HIV-positive couple were compelled to work together on finding a solution that granted them to conceive a healthy baby given that no their options were available (Baylis, 2019).. Of course, life-long treatment for HIV exists, though one must consider the financial and psychological ruin the family would face. Additionally, IVF and PGD may be capable of giving the couple the chance of conceiving a healthy baby, but it is not guaranteed (Baylis, 2019). Ethically speaking, couples are deserving of being presented with all available options that concern the well-being of their prospective child, including the opportunity to permanently eliminate a hereditary condition. Not welcoming this technology because the need for it is limited, since only a fraction of Ari Belotserkovsky 1004909067 04-13-2021 couples do not conceive a healthy baby through PGD and IVF, challenges the moral merits of what biotechnologists work towards when developing new and beneficial biotechnology (Cavaliere, n.d.). Moreover, one may consider that Dr. He was playing the role of god by altering the part of us that encodes our futures. However, it is evident that Dr. He was instead acting as a saviour by preventing the death or debilitating life-long condition that the baby would have endured should it have been conceived naturally. Furthermore, this does not imply that Lulu and Nana are artificial babies; their genomes were modified in the same environment that zygotes are selected in during PGD, and these babies are considered natural. (1) Contemporary Influences on Our Genome Historically, there have been athletes participating in a variety of sports who abused the power of science for their own benefit, that is, temporarily enhancing the expression of their genome to perform better in sports (Paßreiter et al., 2020). This act was termed gene doping, and although now banned, it demonstrates that genetic enhancement, even temporary, exists and is accessible for retail use, since these drugs have actual medicinal purposes (Paßreiter et al., 2020). Despite gene doping not involving the modification of the genome itself, it further demonstrates that the genome can be influenced. Another example of genetic influence are vaccines, which force the individual to produce antibodies against the target foreign entity (Pulendran & Ahmed, 2011). Moreover, the capacity for stem cells to differentiate into any cell type by influencing the expression of certain genes has been utilized for the recovery of burn victims and growing organs for organ transplantation (Cascalho & Platt, 2006; Francis et al., 2019). As such, it is evident that our genomes have the capacity to be influenced by medicinal products and services and they collectively enhance our health by overcoming its weaknesses. The purpose of genetic modification is nothing short of this; to enhance our health and well-being. Ari Belotserkovsky 1004909067 04-13-2021 (2) Genome Modifications in Model Organisms Model organisms are often used in experiments because of their metabolic, genomic, or immune resemblance to humans. As such, these organisms are useful when replicating human-specific diseases. Such organisms are known as chimeras; organisms with genetic or phenotypic characteristics that are inherent to humans (Furtado & Furtado, 2019). Thus, when a hereditary human disease is under research, model organisms are ideal candidates for experimentation. The protocols responsible for replicating hereditary human disease in these organisms involve genetic modification of the mother or embryo, since a hereditary disease must be transferred from mother to offspring (Li et al., 2020). For instance, to produce an animal model that harbours the hereditary disease known as Duchene Muscular Dystrophy (DMD), a zygote must undergo exon splicing of a particular healthy gene using the CRISPR/Cas9, creating the necessary mutation (Li et al., 2020). According to Sui et al., their DMD rabbit model had very similar pathology to that of human patients (Sui et al., 2018). This demonstrates the effectiveness and beneficial utility of embryonic genetic modification; rather than performing the necessary experiments when studying the disease or test developing drugs on humans, they can be tested on these model organisms. Such experiments should be considered ethically permissible because they protect future consumers from any harm that the research could lead to (Ormandy et al., 2011). Of course, the welfare of the animals is also sought after (Ormandy et al., 2011). Alternatively, embryonic gene modification can also be used to cure hereditary diseases. This has been demonstrated in several studies, particularly one in which the CRISPR/Cas9 system reverted the mutation of DMD by slicing off the mutated exon in the embryo of an animal model (Kaiser, 2015). As a proof of concept, this demonstrates that embryonic genome editing has the potential to eliminate hereditary diseases that currently cannot be cure, but only mitigated. From an ethical perspective, it is immoral to prevent the development of such technology when it has the potential to save and improve the lives of countless people. Ari Belotserkovsky 1004909067 04-13-2021 (3) Genome Modification in Humans Dr. He’s human embryonic genome modification experiments were the first to be practically applied in humans. Many of the ethical concerns regarding his experiments are unjustified. For example, some scientists argued that his gene editing experiments were unsafe, that such genetic modifications can result in mutations that may worsen the condition of the babies genome (Savulescu et al., 2015). However, it is obviously unethical to implant an embryo when a high risk of a deleterious mutation persists and there are methodologies that can detect whether such mutations are present, thereby preventing such incidents from ever occurring (Savulescu et al., 2015). As per Savulescu et al., it is unnecessary to implement a moratorium on embryonic genome modifications because it poses a risk to the baby when the moratorium on experiments that pose harmful risk to humans already exists; this would only delay the progression of research and the development of treatments that can cure hereditary diseases in question (Savulescu et al., 2015). Additionally, there are laws in several countries that permit the creation of human embryos for research purposes, but then demand their destruction shortly after, typically after 14 days (Savulescu et al., 2015). If ethical quandary involving the destruction of human embryos after their use in experiments is lacking then, in comparison, the attempts to genetically modify human embryos to cure debilitating diseases should be considered ethically permissible. Furthermore, the 14 day limit to maintain a human embryo is enough to perform human genome modifications and observe the result (Savulescu et al., 2015). One may argue against human embryo genome modifications due to conflicting religious beliefs, but this outlook conflicts with abortion and IVF, which produces an excess amount of embryos (Savulescu et al., 2015). Contrary to IVF, embryonic genome modifications has the potential to reduce the amount of embryos used and destroyed prior to implantation (Savulescu et al., 2015). Ultimately, the moral imperative on human embryo genome modification leans towards being permissible, since it Ari Belotserkovsky 1004909067 04-13-2021 only reflects positive outcomes of health and reduces the amount of embryos that are destroyed prior to implantation. Unfortunately, this moral imperative does not align with some discriminatory beliefs against human genome editing. (4) Intent of Genome Modification The purpose of human embryo genome editing is to eliminate hereditary disease; its utility should not extend to retailers with the desire of creating designer babies. As such, a clear distinction between genome modification and genome enhancement must be made; genome modification must involve a necessity whereas genome enhancement is done out of desire (Baylis, 2019). Since the transition to genome enhancement could potentially occur, this still should not invoke a moratorium on embryonic gene modification. There are plenty of services that have the capacity to transition from medicinal to non-medicinal or nefarious use, but it does not suggest that laws and regulations cannot prevent this from happening. For example, as per Savulescu et al., PGD and IVF have the capacity to be used to select for controversial traits such as intelligence and height, yet a moratorium on these services does not exist (Savulescu et al., 2015). Furthermore, the existence of these services does not suggest that a transition to non-medicinal or nefarious use will occur even with laws and regulations in place; compelling evidence would have to be provided to demonstrate a plausible negative impact of the service on society. In the case of embryonic genome modification, a valid moratorium should require evidence demonstrating that a greater desire for genetic enhancement than genome modifications to cure disease prevails in society. As per Baylis, surveys conducted by the Pew Research Center in 2018 found that 72% of respondents opted for genome modification to cure hereditary disease while only 19% opted for genetic enhancement for a trait such as increased intelligence (Baylis, 2019). Since the intended benefits of embryonic genome modification greatly outweigh the desire for genome enhancement it should be deemed ethically permissible. Ari Belotserkovsky 1004909067 04-13-2021 Conclusions In all, biotechnological innovation continues to progress at an accelerating pace. The possibility that the moratorium on human embryo genome modification is lifted must be accepted, and should this occur a conversation regarding ethical concerns must take place. This research paper has demonstrated why human embryo genome modification as a means to cure hereditary disease should be ethically permissible; multiple factors that influence our genomes already exist, embryonic genome modification is already used in research to create model organisms and study hereditary diseases, a research scientist has demonstrated the utility of this technology by enabling an HIV-positive couple to give birth to genetically modified twins, and the intended benefits of this technology greatly outweigh the risk for its misuse. Ari Belotserkovsky 1004909067 04-13-2021 Literature Cited Baylis, F. (2019). Babies by Design. Altered Inheritance: CRISPR and the Ethics of Human Genome Editing. Cambridge, Massachusetts: Harvard University Press. https://doiorg.myaccess.library.utoronto.ca/10.4159/9780674241954 Cascalho, M., & Platt, J. L. (2006). THE FUTURE OF ORGAN REPLACEMENT—NEEDS, POTENTIAL APPLICATIONS AND OBSTACLES TO APPLICATION. Transplantation Proceedings, 38(2), 362–364. https://doi.org/10.1016/j.transproceed.2005.12.055 Cavaliere, D. G. (n.d.). The Ethics of Human Genome Editing. 19. Correspondent, M. T. B. H. (2019, January 9). Harvard researchers share views on future, ethics of gene editing. Harvard Gazette. https://news.harvard.edu/gazette/story/2019/01/perspectives-ongene-editing/ Francis, E., Kearney, L., & Clover, J. (2019). The effects of stem cells on burn wounds: A review. International Journal of Burns and Trauma, 9(1), 1–12. Furtado, R. N., & Furtado, R. N. (2019). Gene editing: The risks and benefits of modifying human DNA. 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