Big Picture:

CRISPR–Cas9 is an emerging gene editing technology that can be used in the treatment of chronic diseases and cancers. Early research has shown that patients involved in clinical trials have seen improving outcomes because of the technology’s effectiveness. Other uses include engineering plants to withstand the effects of climate change and mutating mosquitos to be less transmissible for  malaria. However, ethical controversies arise when considering the technology’s use in early human germ lines (sex cells). Though it is not fully feasible today to use this technology for genetic enhancement, such as designer babies, the ethical questions this technology generates remains an issue. Equity and accessibility are the primary  ethical implications of the usage of CRISPR-Cas9. Because CRISPR-Cas9 is such a new technology — with the landmark paper having been published in Science in 2012 — the potential for off-target effects and unintended consequences emerging in later years is a concern. In the case of gene enhancement, it is necessary to make sure that introducing these enhancements will not put the embryo at greater risk. As research and clinical trials involving the usage of CRISPR-Cas9 technology continue, further scientific, medical, and ethical implications will likely emerge. It is important to note that this technology has developed quickly and is even available to the average person who, equipped with the necessary biological knowledge, can perform basic CRISPR experimentation through the internet. This information would suggest that there are less serious implications that emerge from CRISPR-Cas9 experimentation. Rather, the ethical questions emerge at the therapeutic and human embryonic levels. The question remains whether regulation or legislation against this technology is necessary to address these implications at such an early period in its development. 

Operative Definitions:

1. Gene Therapy: any process that allows scientists or physicians to treat or prevent a disorder by inactivating a problem gene or by inserting a new gene. CRISPR-Cas9 is considered a form of gene therapy. 
2. Germline Gene Enhancement: a process by which the characteristics or traits of an organism are chosen according to the interests of the agents involved during its gestation. 
3. CRISPR-Cas9: According to researchers at Cold Spring Harbor Laboratory, this is “gene editing technology [that] involves using clustered regularly interspaced short palindromic repeats (CRISPR) found in bacteria.” It introduces, edits, or deletes the DNA sequence of an organism, during or after its gestation. 

Important Statistics and Facts:

1. According to McKinsey Global Institute (MGI), a bio-revolution has emerged in the last few decades, with advancements in both biological technology and data science. The scope of this wave of innovation suggests that 60% of the world economy’s physical outputs are already biological or could become produced by biological processes in the future. 
2. As much as 70% of the bio-innovation wave’s output falls under strict regulation, according to MGI.
3. MGI also estimates that 70% of the reduction of disease in the next 10-20 years will be in higher income countries, though they only make up 30% of the worldwide disease burden. 
4. Emergen Research found that the global gene editing market size was $5.20 billion in 2020 and is forecasted to reach $18.50 billion by 2028. 

3-Point Plan:

1. The federal government, alongside private institutions, should continue to allocate funding towards further research on CRISPR-Cas9 and genetic editing, especially in order to determine the severity of off-target effects, if any. The FDA should consider the findings of such research in their regulation of this emerging technology. A novel technology like CRISPR-Cas9 presents many potential benefits to society. However, it must be thoroughly evaluated to ensure its safety for use in human populations. Research institutions within  universities  and private laboratories, and even pharmaceutical companies, require high levels of funding to conduct such research. This cost burden must be met in part by federal and state governments, for research on both animal models and humans. Clinical trials, which are overseen by the federal government, should be sure to meet ethical requirements so that there are no setbacks in assessing and regulating these technologies.
2. Therapeutic use of CRISPR-Cas9 in humans should remain at the clinical trial level until 2025, at the least. There are a number of conditions currently being treated with CRISPR-Cas9 in clinical trials. For research to reach the point of being done on human participants, animal models must have been conducted and have met certain safety criteria. The potential for off-target effects, however, remains an issue, especially when considering the broad range of diseases being studied and their genetic nature. It is essential for CRISPR research to remain in clinical trials until at least 2025 to address this issue. Such a measure is especially supported by the Covid-19 pandemic’s disruption of research. Though this might set back the development and treatment timeline that currently exists, and though some trials might be ready to move forward to regulating therapeutic treatment using CRISPR, it is essential for scientists and physicians to be confident in this treatment’s efficacy and safety.
3. Experts of medical ethics, scientists, physicians and lawmakers should work together to inform any regulation or legislation that might in the future govern CRISPR-Cas9 use or research at the federal or state levels. They should especially consider the ethical implications of using gene editing technologies for genetic enhancement purposes. When a technology as novel and monumental as CRISPR-Cas9 emerges, a variety of stakeholders also emerge. These can include research institutions (colleges and universities, for example), scientists and physicians, manufacturers, pharmaceutical industry, ethicists and legislators. It is essential to ensure that all bodies have a place at the regulatory table and that any regulation is informed scientifically, ethically, and economically. This is especially important in considering the technology’s use on germ lines and genetic enhancement, which could be a powerful tool that would allow individuals with greater wealth to have a high advantage over the rest of the population. The government should not make a strict or lenient decision until research has adequately informed such legislation. 

Why This Initiative is Important:

When a treatment is developed for a single disease or condition, it must be thoroughly evaluated for its efficacy. When a technology like CRISPR-Cas9, which has the potential to treat a multitude of conditions, emerges, it is essential to make sure that it is efficacious at all levels and in all patients. The use of CRISPR technology as a therapy to treat genetic diseases is commonly accepted; however, its use as a means of genetic enhancement - especially in the case of the ethical question of designer babies - remains to be seen. There exist a number of ethical, scientific, technological, and economic implications that could arise from the use of this technology for genetic enhancement reasons that do not exist when using the treatment as a gene therapy for a genetic disease. A potential low-to-moderate risk for off-target effects might be justified in a patient with a malignant or fatal cancer, but not for an embryo for which parents would desire to choose certain characteristics or traits (blue eyes, intelligence, athleticism, etc.). It is necessary to evaluate the potential risks this technology poses and also to determine the ethical implications of genetic enhancement. 

Acknowledgments:

 The following student worked on this nonpartisan proposal: Sahiti R. Karnati, Columbia University, Mailman School of Public Health.

Note: Not all participants agree with every aspect of this proposal. To arrive at a proposal that takes multiple views into account requires compromise and difficult decisions. For individual commentary on this proposal and more detail, go to ournationalconversation.org. We invite you to add your comments as well.

Works Cited: 

Angelakos, Christopher C., and Ted Abel. “Molecular Genetic Strategies in the Study of Corticohippocampal Circuits.” Cold Spring Harbor Perspectives in Biology, vol. 7, no. 7, July 2015, https://doi.org/10.1101/cshperspect.a021725. 

Balch, Bridget. “The Future of CRISPR Is Now.” AAMC, Association of American Medical

Colleges , 2 Dec. 2021, www.aamc.org/news-insights/future-crispr-now. 

Cyranoski, David. “The CRISPR-Baby Scandal: What's next for Human Gene-Editing.” Nature

News, Nature Publishing Group, 26 Feb. 2019, www.nature.com/articles/d41586-019-00673-1. 

Evers, Matthias, and Michael Chui. “The Promise and Peril of the Bio Revolution.” McKinsey &

Company, McKinsey & Company, 26 Jan. 2021, www.mckinsey.com/mgi/overview/in-the-news/the-promise-and-peril-of-the-bio-revolution. 

“Gene Editing Market Size to Reach USD 18.50 Billion in 2028: Industry Trend – Extensive Use of

Gene Editing in Development of Personalized Medicine.” BioSpace, BioSpace, 15 Feb. 2022, www.biospace.com/article/gene-editing-market-size-to-reach-usd-18-50-billion-in-2028-industry-trend-extensive-use-of-gene-editing-in-development-of-personalized-medicine/. 

“United States: Therapeutic / Stem Cell - Global Gene Editing Regulation ...” Global Gene Editing

Regulation Tracker, Genetic Literacy Project, www.crispr-gene-editing-regs-tracker.geneticliteracyproject.org/united-states-gene-therapy-stem-cells/.