Asserting the Autoimmune Need for Genetic Intervention (Apr 20, 2022)

      It is understandable that public opinion regarding gene editing technology such as CRISPR remains generally wary and distrustful. Not only does CRISPR’s relative novelty compared to established medical treatments impact public perceptions of its safety and effectiveness, but controversies surrounding its limitations and ethical uses further fuel negative responses. While these fears can be healthy and reasonable, it is unreasonable that they should completely impede beneficial medical advancements – nor should those fears attempt to assert that current approaches to medical treatment cannot be improved upon when studies show the opposite. Research into autoimmune diseases such as Hashimoto’s disease not only support the necessity for treatment reform, but also reveal that CRISPR shows promising potential to become a groundbreaking treatment for various autoimmune diseases. More forward thinking, CRISPR could one day have the power to remove the hereditary aspect of autoimmune diseases to end the cycle of familial disease at its source. CRISPR has the potential to treat and prevent autoimmune diseases more effectively than currently available medical treatments, thus necessitating further research and funding into CRISPR’s development despite public fears.

            While autoimmune diseases are often considered “manageable” with medical treatment, research shows that those living with inflammatory illnesses often suffer despite medical intervention more than the able-bodied population realizes. Min Ho Lee and colleagues’ outline the consequential nature of having an autoimmune disease, stating that “autoimmune diseases occur in up to 3-5% of the general population, and they decrease life expectancy… [as well as being] associated with mood disorders and impaired quality of life” (Lee et al, 2022). Autoimmune diseases are chronic, meaning that millions of patients diagnosed with autoimmunity across the globe are dependent on medical treatment for the rest of their lives to manage their disease and alleviate debilitating symptoms. But current medications leave much to be desired. A 2021 survey on adults with hypothyroidism conducted by the British Thyroid Foundation found that “over three quarters (77.6%) of respondents felt dissatisfied with their treatment [and reported low quality of life]” (Mitchell et al, 2021). The United States did not fare much better, with the American Thyroid Association reporting similar findings in 2017 that show high amounts of impaired quality of life and low scores of satisfaction with treatment options in those with hypothyroidism (ATA, 2017). Keeping in mind that Hashimoto’s disease, an autoimmune disease that causes hypothyroidism, is incredibly common and regarded as one of the most “manageable” autoimmune disorders, these reports have startling and unsettling implications into the failures of current medical care and technology to adequately improve the lives of patients with autoimmunity. This is what Lee’s research would categorize as representative of “the growing need for gene-editing therapeutic approaches” (Lee et al., 2). More advancements are needed to help people with autoimmunity lead normal, pain-free lives. CRISPR can do just that – but only if we let it.

Doctors and researchers behind the “Gene Editing for Inflammatory Diseases” study believe CRISPR has the potential to fill the holes that exist within the healthcare system: first by expanding understanding into the “biology of inflammatory disease” (Ewart et al., 13) and second through “its ability to orchestrate precise targeted modifications to the genome [to enable] cell-based therapies” (Ewart et al., 6). By being able to repair variations within the genomes, doctors can gain a more comprehensive understanding of how cells that cause autoimmune diseases are triggered and how they respond to inflammatory stress. The more understanding that doctors have as to the nature of autoimmune diseases, the easier it will be to knock out the genes responsible for triggering or worsening the progression of these diseases. In fact, this has already taken place within some experiments. Lee’s study demonstrates that the “inactivation of MyD88 adapter protein by CRISPR-Cas9 reduced the activity of differentially expressed genes inducing the expression of IL-1B and IL-36G… [which is a gene] family that may play an important role in the development of autoimmune diseases” (Lee et al., 4). This is a fundamental finding; if research shows that it is possible to suppress the activation of autoimmune diseases as part of gene editing treatment, there is a strong possibility that within the near future autoimmune diseases can become a thing of the past. This outcome is considered all the more likely when reminded that many autoimmune diseases “feature heritable components” (Ewart et al., 6), meaning that if doctors and scientists can narrow down triggers to specific cells then it can be removed from the germline to prevent it from being passed on to the next generation. In a short few decades, CRISPR demonstrates the ability to nearly eradicate familial autoimmunity whereas current medications and treatments fail to bring significant improvement to patients.

The limitations and holdbacks of CRISPR cannot be ignored in blind favor of its benefits, however. Lee cites that “many of the studies on the treatment of autoimmune diseases using CRISPR/Cas9 have been conducted in cell studies so far and, therefore, more studies in humans are needed” (Lee et al., 10). Conducting these studies within humans can pose an ethical issue when scientists are still concerned about “off-target activity” (Lee et al., 10), when genes other than the targeted one are unwittingly affected or manipulated to the potential detriment of the organism. While this concern is valid, Ewart’s research asserts that work is already in progress to “enhance specificity to the intended target site” (Ewart et al., 9) and the study regarding gene suppression cited in Lee’s research suggests scientists are on the verge of safe human trials with gene editing technology. Improvements in autoimmunity seen in animal studies, such as those with mice, also prove that these studies are worth taking place with well-informed and voluntary human subjects. Another source of hesitancy and ethical conflict with CRISPR involves the editing of germline cells. Any changes made to reproductive cells, foreseeable or otherwise, will become inherited by succeeding generations. If a worst-case scenario occurs, unintended variations or off target activities result in a permanent change of that bloodline with long-term, just as unforeseeable consequences. While the reality and weight of gene editing can be daunting, it can be argued that it is just as unethical to not pursue advancements in CRISPR technology when it shows much potential to decrease suffering and disease. Our fears and apprehension can be used productively to ensure future research with gene editing in humans is, in fact, humane and safe and ethical. They do not have to limit us. Because ultimately, it should be the choice of those with autoimmune diseases or those possessing a family history of autoimmune diseases to decide whether they believe the benefits outweigh the risks. The choice should not be taken away by those who cannot grasp their lived experiences or see the literal life changing qualities CRISPR possesses.

I was diagnosed with Hashimoto’s disease in the fall of 2021. Thyroid issues run within the women in my family. I will never be able to have a “normative” experience because my disease robs me of so much – of a functioning thyroid gland that controls my metabolism, my energy, my ability to live pain free, my cognitive functions, and my mental health. My medication, levothyroxine, has helped bring my thyroid levels back to normal. But my symptoms still persist with fluctuating intensity. I often wonder how different my life would be if medical intervention had happened sooner in my life. Sometimes I wonder how different of a person I would be if I did not have Hashimoto’s disease at all. I may never know how drastically my life would differ. But CRISPR provides a unique and unchallenged opportunity to come the closest to the “normal” experience that I can. One day I could provide my future child with the chance I never had to be healthy and uninhibited. They will only have that chance if society recognizes the potential of CRISPR and pursues its research with healthy optimism and healthy fear.

 

Works Cited

American Thyroid Association. “ATA Survey of Patients with Hypothyroidism Shows Dissatisfaction with Treatment Options.” American Thyroid Association, 8 May 2018, https://www.thyroid.org/ata-hypothyroidism-survey-results/.

Ewart, David T., et al. “Gene Editing for Inflammatory Disorders.” Annals of the Rheumatic Diseases, vol. 78, no. 1, Jan. 2019, pp. 6–15. EBSCOhost, https://doi.org/10.1136/annrheumdis-2018-213454.

Lee, Min Ho, et al. “Genome Editing Using CRISPR-Cas9 and Autoimmune Diseases: A Comprehensive Review.” International Journal of Molecular Sciences, vol. 23, no. 3, Feb. 2022, p. 1337–N.PAG. EBSCOhost, https://doi.org/10.3390/ijms23031337.

Mitchell, Anna L., et al. “Patient Satisfaction and Quality of Life in Hypothyroidism: An Online Survey by the British Thyroid Foundation.” Clin Endocrinol, 94: 513-520. 2021. https://doi.org/10.1111/cen.14340