Camille Castelyn

This article provides ethical guidance on using race in health research as a variable or in defining the study population. To this end, a plain, non-exhaustive checklist is provided for researchers and research ethics committees, preceded by a brief introduction on the need for justification when using race as a variable or in defining a study population, the problem of exoticism, that distinctions pertain between race, ethnicity and ancestry, the problematic naming of races, and that race does not serve well as a presumed biological construct in genetic research.

Photo by Jonathan Ford on Unsplash ABSTRACT Since 2008, an average of twenty million people per year have been displaced by weather events. Climate migration creates a special setting for a duty to rescue. A duty to rescue is a moral rather than legal duty and imposes on a bystander to take an active role in preventing serious harm to someone else. This paper analyzes the idea of expanding a duty to rescue to climate migration. We address who should have the duty and to whom the duty should extend. The paper discusses ways to define and apply the duty to rescue as well as its limitations, arguing that it may take the form of an ethical duty to prepare.

Photo by National Cancer Institute on Unsplash INTRODUCTION More than 20 cell and gene therapies are now available to safely minimize genetic diseases such as retinal dystrophy, some B-cell lymphomas, and B-cell lymphoblastic leukemia.[1] One such gene-editing tool is Clustered Regular Inter Spaced Palindromic Repeats and its associated proteins or CRISPR-Cas. Jennifer Doudna and Emmanuelle Charpentier described CRISPR’s potential as an accurate genome editing tool in 2012. The FDA approved the first cell and gene therapy in 2017.[2] The FDA is continually approving more CRISPR clinical trials, including therapies to treat sickle cell anemia, cancer, and HIV.[3] Amid the COVID-19 pandemic, the broad potential applications of CRISPR have extended beyond gene editing. CRISPR is being used in rapid diagnostic testing to determine not only whether an individual becomes infected with SARS-Cov-2 but also the specific variant.[4] As with many diagnostic tests, scientists still face challenges like speed, sensitivity, and robustness. Nonetheless, these tests could revolutionize surveillance of the virus and help curb the spread of new variants as they arise. According to the Centers for Disease Control and Prevention, there are SARS-CoV-2 variants of interest, variants of concern, and variants of high consequence. In varying degrees, these may impact the efficacy of different vaccines and treatment plans.[5] Knowing which variant an individual has or is circulating within a population informs public health policy. l. Public Perceptions of Gene Editing Throughout the Decades Perceptions about gene editing have fluctuated, especially since the 1970s. Support has varied for recombinant DNA in which editing a bacterial genome produces human insulin to treat diabetes, genetically modified plants such as antibiotic-resistant tobacco, and other genetically modified organisms. Human gene editing has a tainted past: consider the teenager Jesse Gelsinger who tragically died in a gene therapy clinical trial in 1999.[6] Another gene therapy trial led to the development of leukemia in several young children.[7] In the last two decades, there have been significant improvements in safety and reliability. Though scientists have developed various gene therapies over the years, such as viral vector delivery of therapeutic transgenes, transcription activator-like effector nucleases, and zinc finger nucleotides, CRISPR far surpasses them by safety, accuracy, and ease of use.[8] ll. Shifting Perceptions and Broader Applications CRISPR is controversial due to concerns of safety, misuse for non-therapeutic purposes, and uncertainty about the science and technology. Yet, there is also an underlying assumption that gene editing for therapeutic purposes would be a good use of CRISPR. There is an ethical imperative to use CRISPR therapeutically to safely reduce suffering for people with debilitating genetic diseases if proven safe. However, there is more variation in what would be considered good about uses beyond therapeutic applications, such as enhancement purposes. Enhancement is a broad and conceptually laden term. For example, Julian Savulescu defines enhancement as any change in the person’s state – biological or psychological – which in turn is experienced or judged by the person or people as good.[9] Thus, enhancement could include any gene-editing relating to physical, cognitive, aesthetic, or moral enhancement. For example, the public and the scientific community reacted with outrage to the 2018 scandal of He Jiankui, a Chinese scientist who gene-edited two baby girls to make them HIV resistant. Rather than therapeutic gene-editing, this example was widely considered enhancement. The public may perceive the uses of CRISPR for enhancement as negative, but improved public perception of CRISPR overall would be beneficial to promote its therapeutic uses. CRISPR opened an array of possibilities and consequential decisions that lie in the hands of the consumer. A qualitative study done to gauge opinions on Twitter found that “#CRISPR babies” elicited responses of sentiments ranging from positive and neutral to negative, spiking in 2018 with mostly neutral and negative sentiments.[10] As cell and gene therapies move to market treating a small number of people with rare genetic diseases, public perceptions of these technologies are already shifting and may shift more over time. The factors influencing this shift toward acceptance might include trust in science,[11] trust in the technology or the brand[12] that brings it to market, and proven safety and efficacy over time. Meanwhile, in this COVID-19 pandemic, CRISPR's beneficial services for the detection of different variants in individuals and populations may positively impact the way it is perceived and accepted by the public. Mammoth Biosciences [13] and Nanyang Technological University have developed rapid diagnostic tests called DETECTR and VaNGuard, respectively, to detect variants.[14] CRISPR and its associated proteins act as molecular scissors that have the ability to cut a specific section of genetic material with accuracy. It is the exploitation of a bacterial defense mechanism. When a virus infects bacteria, it uses CRISPR-associated proteins to cut out the bacteriophage’s RNA. The bacteria then insert some of the virus RNA into its own genome to detect and destroy it in the future. In the VaNGuard diagnostic test, the enzyme enAsCas12a targets specific sections of the SARS-CoV-2 genome. Guided by two guide RNAs, it snips a section of the virus and can detect the virus as well as two mutation sites in the virus. CONCLUSION CRISPR’s application as a diagnostic testing tool is different from its gene-editing use. However, people may not distinguish the different applications when forming their perceptions of CRISPR. Public confidence in certain technology needs only a push in a certain direction to sway opinion toward mass consumption or disapproval. Research investigating people’s perceptions is becoming central to the debates about new technologies.[15] The WHO’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, in their Position Paper, calls for “education, engagement, and empowerment.”[16] They call on the United Nations to establish an interagency working group to facilitate global dialogue. The National Academies of Sciences, Engineering, and Medicine Consensus Study Report, also calls for public engagement and education about these technologies.[17] DIY and biohacking communities have shown an inclination to understand and apply these technologies with or without the guidance of regulators, scientists, or academia.[18] Perhaps as CRISPR is used to saved lives during the pandemic, this is a pivotal moment to educate people about CRISPR and its broad applications. [1] “Approved Cellular and Gene Therapy Products,” Food and Drug Administration, June 15, 2021, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products. Jim Daley, “Gene Therapy Arrives,” Scientific American, January 1, 2020, https://www.scientificamerican.com/article/gene-therapy-arrives/. [2] Broad Institute, “CRISPR Timeline,” n.d., https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline. “Who Owns CRISPR in 2021? It’s Even More Complicated Than You Think,” April 27, 2021, https://synbiobeta.com/who-owns-crispr-in-2021-its-even-more-complicated-than-you-think/. [3] Robert Sanders, “FDA Approves First Test of CRISPR to Correct Genetic Defect Causing Sickle Cell Disease,” March 30, 2021, https://news.berkeley.edu/2021/03/30/fda-approves-first-test-of-crispr-to-correct-genetic-defect-causing-sickle-cell-disease/. Laura Brzyski, “Excision BioTherapeutics Has Secured $60M to Proceed with HIV Clinical Trial,” Philadelphia Magazine, March 5, 2021, https://www.phillymag.com/healthcare-news/2021/03/05/excision-biotherapeutics-temple-hiv-clinical-trial/. [4] “A COVID-19 Test to Detect Virus Variants,” Nanyang Technological University, March 29, 2021, https://www.ntu.edu.sg/news/detail/a-covid-19-test-to-detect-virus-variants. [5] “SARS-CoV-2 Variant Classifications and Definitions,” Centers for Disease Control and Prevention, July 13, 2021, https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html. [6] Nature, “Gene-therapy trials must proceed with caution,” Nature 534, 590. https://doi.org/10.1038/534590a. [7] Fathema Uddin, Charles M. Rudin, and Triparna Sen, “CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future,” Frontiers in Oncology 10 : 1387, doi:10.3389/fonc.2020.01387. [8] Ibid. [9] Savulescu, J, “Ethics and Enhancement,” Annals New York Academy of Sciences, 321-338. [10] Martin Müller et al., “Assessing Public Opinion on CRISPR-Cas9: Combining Crowdsourcing and Deep Learning,” Journal of Medical Internet Research 22, no. 8 : e17830, doi:10.2196/17830. [11] Stephan Guttinger, “Trust in Science: CRISPR–Cas9 and the Ban on Human Germline Editing,” Science and Engineering Ethics 24, no. 4 : 1077–96, doi:10.1007/s11948-017-9931-1. [12] Katherine Mobley, “How Public Perception Can Make Or Break A Brand, And What It Means For Employees,” Forbes, January 5, 2019, https://www.forbes.com/sites/forbescommunicationscouncil/2019/05/01/how-public-perception-can-make-or-break-a-brand-and-what-it-means-for-employees/?sh=7b81058ad118. [13] James P. Broughton et al., “CRISPR–Cas12-Based Detection of SARS-CoV-2,” Nature Biotechnology 38, no. 7 : 870–74, doi:10.1038/s41587-020-0513-4. [14] “A COVID-19 Test to Detect Virus Variants.”; Kean Hean Ooi et al., “An Engineered CRISPR-Cas12a Variant and DNA-RNA Hybrid Guides Enable Robust and Rapid COVID-19 Testing,” Nature Communications 12, no. 1 : 1739, doi:10.1038/s41467-021-21996-6. [15] Dietram A. Scheufele et al., “What We Know about Effective Public Engagement on CRISPR and Beyond,” Proceedings of the National Academy of Sciences 118, no. 22 : e2004835117, doi:10.1073/pnas.2004835117. [16] WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, “Humane Genome Editing Position Paper”. [17] International Commission on the Clinical Use of Human Germline Genome Editing et al., Heritable Human Genome Editing, doi:10.17226/25665. [18] Josiah Zayner, “2018 Genetic Engineering For All: The Last Great Frontier of Human Freedom,” www.leapsmag.com, January 20, 2018, https://leapsmag.com/genetic-engineering-last-great-frontier-human-freedom/particle-1.

In January 2020, during China’s COVID-19 outbreak, the NASA Earth Observatory captured aerial images indicating significantly lower emissions of nitrogen dioxide, a major air pollutant, across China’s mainland.[1] Scientists across the globe have reported preliminary empirical data that amid shelter-in-place directives and the shutting down of large-scale economic activity, the environment is flourishing. Abnormal sightings of wild animals roaming freely in deserted cities have been widely reported. For example, monkeys in Lopburi, Bangkok and leatherback turtles on deserted beaches in Florida, US are thriving.[2] This pandemic has given mother earth a chance to ‘breathe.’ Environmentalists are asking how long the breather will last and whether it will sustain the earth for years to come, when business as usual returns bringing environmental challenges. This pandemic has shaken up business as usual including major economic drivers of supply and demand. At the moment, the demand for oil is at an all-time low whereas personal protective equipment markets are booming. The world has entered into a recession, with estimates of a US $2 trillion loss. Approximately 11 million people are being pushed into poverty.[3] People are functioning differently: there is a shift toward working remotely, micro gardening in urban settings, more mindful use of resources, and spending more time at home with friends and family. These trends may put less strain on people as well as on the environment. As people find a better work-life balance and commute less, the 77.5% of pollution caused by car and air travel, may be reduced.[4] Some scientists also argue that if the planet were healthier we would see fewer viruses take hold.[5] Although scientists estimate that the impact of COVID-19 on the environment may be temporarily positive, long-lasting action and commitment are necessary to mitigate climate change. The Sustainable Development Goals adopted by United Nations member states in 2015 aim to achieve climate action, sustainable cities, and sustainable use of the earth and ocean’s resources by 2030. While there is a short-term environmental benefit of lower emissions, the long-term goals may be set back due to the COVID-19 pandemic.[6] The SDGs include eliminating poverty, protecting the planet, and ensuring prosperity and peace for all people.[7] The SDGs are a stark reminder that the pre-COVID-19 world was far from perfect. Most countries’ economies are driven by exponential capitalist growth in which the environment and people are exploited for the sake of profit. Nearly half the world lives on less than $5.50 a day.[8] 44 percent of the world’s net worth belongs to 0.8 percent of the world’s individuals[9]. This crisis has exposed systemic flaws even more, as those who have lower socio-economic standing are disproportionately affected by this pandemic. They are more susceptible because they do not have access to basic sanitation and are often forced to live in places affected worse by climate change and pollution. In 2019 Greta Thunberg, the 15-year-old environmental activist, made the case that the economics to solve the current environmental constraints did not yet exist. In 2020, amid the pandemic, the United Nations reported that there is a need to rebuild economies differently.[10] Individuals and governments may be spurred to change their approach to climate action requiring a shift of societal norms to value the environment and people’s happiness more than profit growth. In Amsterdam, donut economics will be used to help the economy recover.[11] Donut economics originated from Kate Raworth of Oxford University’s Environmental Change Institute’s book, ‘Donut Economics: seven ways to think like a 21st century economist.’ The inner ring of the donut refers to the minimum that people need to live a good life, which is based on the UN’s SDGs. Any person who does not have access to these minimum standards of living is described as living in the doughnut’s hole. The outer ring of the doughnut, where the sprinkles go, represents the ecological outer parameters, drawn up by earth-system scientists. These outer parameters delineate the boundaries which humanity should not progress beyond if it is to avoid damage to the ozone layer, oceans, freshwater resources, and abundant biodiversity. In developing countries such as South Africa, the opportunity to rebuild the economy by means of donut economics seems idealistic because a large percentage of the population lives inside the doughnut hole. The immediate challenges of debt, poverty, and food shortage brought about by the COVID-19 lockdown are pressing.[12] However, visionary leaders should take a long-term perspective as there is opportunity to do so now. For example, during this time President Cyril Ramaphosa aims to reduce the number of ‘people living inside the donut’s hole’ by improving housing infrastructure in rural areas. Rebuilding a more ethical post-COVID-19 world of both environmental and human flourishing[13] will require a planetary health perspective.[14] The Lancet[15] suggests that a planetary perspective must move beyond an emergency response toward resilience and prevention planning. In “Happiness explained: What human flourishing is and what we can do to promote it,” Paul Aland explains that the principles of human flourishing are fairness, autonomy, community, and engagement. These principles may be the pillars for post-COVID-19 environmental policies. Amid the chaos and trauma of this pandemic, it is up to individuals, leaders, scientists, and bioethicists to take a breather to reflect. It is time to dare to imagine what human and environmental flourishing may look like in a more sustainable post-COVID-19 world and start rebuilding it one step at a time. Photo by RawFilm on Unsplash [1] “These Satellite Photos Show How COVID-19 Lockdowns Have Impacted Global Emissions,” World Economic Forum, March 25, 2020, https://www.weforum.org/agenda/2020/03/emissions-impact-coronavirus-lockdowns-satellites/. [2] Harry Kretchmer, “These Locked-down Cities Are Being Reclaimed by Animals,” World Economic Forum, April 17, 2020, https://www.weforum.org/agenda/2020/04/covid-19-cities-lockdown-animals-goats-boar-monkeys-zoo/. Deena Robinson, “Endangered Sea Turtles Thriving Amid COVID-19 Restrictions,” April 20, 2020, https://earth.org/endangered-sea-turtles-thriving-amid-covid-19-restrictions/. [3] World Economic Forum, “Why We Cannot Lose Sight of the Sustainable Development Goals during Coronavirus,” April 23, 2020, https://www.weforum.org/agenda/2020/04/coronavirus-pandemic-effect-sdg-un-progress/. [4] Hiroko Tabuchi, “‘Worse Than Anyone Expected’: Air Travel Emissions Vastly Outpace Predictions,” The New York Times, September 19, 2019, https://www.nytimes.com/2019/09/19/climate/air-travel-emissions.html. [5] “First Person: COVID-19 Is Not a Silver Lining for the Climate, Says UN Environment Chief,” United Nations News, April 5, 2020, https://news.un.org/en/story/2020/04/1061082. [6] The World Bank, “Poverty,” April 16, 2020, https://www.worldbank.org/en/topic/poverty/overview. [7] United Nations Development Programme, “What Are the Sustainable Development Goals?,” 2015, https://www.undp.org/content/undp/en/home/sustainable-development-goals.html. [8] The World Bank, “Nearly Half the World Lives on Less than $5.50 a Day,” October 17, 2018, https://www.worldbank.org/en/news/press-release/2018/10/17/nearly-half-the-world-lives-on-less-than-550-a-day. [9] James Davies, Rodrigo Lluberas, and Anthony Shorrocks, “Global Wealth Report 2018,” Credit Suisse Research Institute, 2018. [10] “First Person: COVID-19 Is Not a Silver Lining for the Climate, Says UN Environment Chief,” United Nations News, April 5, 2020, https://news.un.org/en/story/2020/04/1061082. [11] Daniel Boffey, “Amsterdam to Embrace ‘doughnut’ Model to Mend Post-Coronavirus Economy,” April 8, 2020, https://www.theguardian.com/world/2020/apr/08/amsterdam-doughnut-model-mend-post-coronavirus-economy. [12] A van den Heever et al., “South Africa Needs a Post-Lockdown Strategy That Emulates South Korea,” The Conversation, April 18, 2020, https://theconversation.com/south-africa-needs-a-post-lockdown-strategy-that-emulates-south-korea-136678. “‘People Need to Eat’: South Africa Eases Coronavirus Lockdown,” Aljazeera, January 5, 2020, https://www.aljazeera.com/news/2020/05/eat-south-africa-eases-coronavirus-lockdown-200501072927207.html. [13] Rose Deller, “Book Review: Happiness Explained: What Human Flourishing Is and How We Can Promote It by Paul Anand,” The London School of Economics and Political Science, August 24, 2016, https://blogs.lse.ac.uk/lsereviewofbooks/2016/08/24/book-review-happiness-explained-what-human-flourishing-is-and-how-we-can-promote-it-by-paul-anand/. [14] Alistair Brown and Richard Horton, “A Planetary Health Perspective on COVID-19: A Call for Papers,” The Lancet 395 : 1099. [15] Brown and Horton.