Advancing the Frontiers of Medicine

CRISPR Technology

By Cal Blevens and Nathan Soltz

CRISPR is a new scientific study that involves changing the genetic code of an individual. Changing someone’s genes could have a major impact on a person’s life. CRISPR uses small strands of RNA and an associated protein to cut recipient DNA at a precise spot (Vogal, 2018). This RNA, called guide RNA (gRNA), binds to the DNA sequence creating a DNA-RNA hybrid (Babacic, 2019).This gRNA-DNA complex is specifically recognised by the cas9 protein (the effector domain), which induces a double-stranded break in the DNA (Babacic, 2019). Genome modification occurs, mainly through activating one of the two DNA repair mechanisms: non-homologous end joining (NHEJ) or homology directed repair (Babacic, 2019). By binding to the DNA, dCas9 prevents transcription factors and other molecules from accessing the sequence, thereby preventing transcription of that gene to mRNA and subsequent translation to protein. Furthermore, dCas9 can be modified with mutations that allow it to bind to other transcription modulators and result in epigenetic activation/silencing (Babacic, 2019). Cas are CRISPR associated proteins. CRISPR is able to produce mutations in genes at a much faster rate than before and is much more cost efficient than past gene-editing techniques (Vogal, 2018). CRISPR is also able to send its mutated genes to the offspring of the organism. CRISPR-cas originate in bacteria and serve as part of the immune system of bacteria and Archaea, used to defend themselves from bacteriophages (Babacic, 2019). Using CRISPR in biotechnology, can in theory change someone’s genetic code to protect them from diseases. However, there are some risks. Risks like if criminals get their hands on this technology and are able to create diseases that are untreatable and cause a mass amount of deaths. While many people are worried about this potential crisis, there is little evidence that supports a terrorist organization would try biochemical warfare (Vogal, 2018). While the technology itself may be simple to handle there are still other factors we need to take into account, technological, social, political, organizational, and economic hurdles that prevented the development of viable weapons in other countries (Vogal, 2018). The studies being conducted now are by scientists that have no interest in creating biochemical warfare and want to keep this technology out of evil hands. These studies are showing a positive sign to be able to change the genetic code in animals, but there are still things we need to think about when trying to implement CRISPR into the medical field.

CRISPR seems to be very effective at editing skeletal muscle DNA and improving specific defects in the mouse test subjects (Babacic, 2019). Model, CRISPR-cas9-mediated dystrophin restoration improved the functionality of the dystrophin-glycoprotein complex by ameliorating localization of proteins, thus recuperating sarcolemmal integrity (Babacic, 2019). Thus, in mice that suffered muscular dystrophy, scientists have been able to go into the skeletal muscle, and improve the proteins so they were not suffering from that disease anymore, with some reports of up to 90 percent of mice being completely healed (Babacic, 2019). Scientists are still learning if they will have the same results in mice for heart muscle cells, but early indications say that they are able to improve the conditions of those cells as well (Babacic, 2019). Among incurable neurological monogenic diseases, Duchenne’s muscular dystrophy (DMD) is the front-runner in the preclinical development of CRISPR-cas systems for therapeutic purposes (Babacic, 2019). Based on to the current pace of development DMD is likely to be the first one to reach clinical phase. DMD, a sex-linked, recessive disease, affects 1 in every 3,500 to 5,000 boys (Babacic, 2019). Figuring out a cure for this horrible disease would end a lot of boys suffering, would really put CRISPR on the map in the medical field, and would provide a good start to proving to people that changing someone’s genetic code can improve their lives.

Does creating this technology create a world where criminals get their hands on this and create a disease that becomes untreatable and kills millions? Creating something this powerful could end up in the wrong ends and would want to kill people. Since most scientists can use CRISPR, if evil scientists want to hurt people they could create something that could be airborne and change the genetic code with no cure. While this technology can improve countless lives it can also hurt and kill people, so while looking to further progress this technology we need to make sure we keep people safe and have it stay out of the wrong peoples hands. This is not the biggest ethical concern since this type of technology would be hard to obtain for terrorist organizations. Another concern we must think about is are we violating people’s religions with this medical advantage? Some people might not want their genetic code changed or that it is not God’s work, so we have to be careful not to change someone’s way of living to heal them. If there religion does not allow for this type of medicine, then we cannot perform it. Another thing to think about is how it will affect the economy system. This technology could create an even larger gap in health care where only the rich can have their DNA changed and healed. There are many things you must think about when changing someone’s genetic code, some questions are harder than others, but if it can save lives it is an option we must take a closer look at.

In the past, other gene editing techniques would cause mutations in the wrong DNA strands or cells. However, the CRISPR-Cas9 system is lowering the risk of off-target damage to practically nothing. In animal models, CRISPR-Cas9 is hitting the intended target and is only affecting the cells or DNA that scientists have designed it to hit. For example, a study conducted by Thomas, et al. demonstrated that efficient CRISPR gene editing was possible without a significant increase in de novo mutation rates, supporting the development of CRISPR-Cas9 as a therapeutic tool (Thomas, 2019). Many studies using CRISPR have been effective at curing diseases inside the test mice (Babacic, 2019). Is it time to begin testing it on humans?

There are several ethical implications to consider when discussing using CRISPR technology. While some of these questions are rooted in religion, there are still many to take into account regardless of religious implications. As far as religious matters go, that is something for a person to consider between themselves and their faith tradition and religious leaders. However, there are other philosophical considerations which are not religiously-based. Perhaps the most central of these is whether people have the innate right to alter their natural biology. Philosophers have considered points similar to this regarding a person’s bodily autonomy which are applicable to this discussion as well.

A person’s autonomy and right to their own body is a topic which has been considered at length by John Rawls. While Rawls’ main area of consideration was political philosophy, he based his philosophy around a certain degree of bodily autonomy. Rawls believed that people had the exclusive right to their own bodies and, to that extent, to do to them what they wished to do to them insofar as it didn’t affect others (1999, pp. 24-25). As such, the utilization of CRISPR to alter one’s own genetic code would be perfectly allowable. Additionally, in the case that CRISPR technology is used to defend against certain diseases such as cancers, the argument could be made that people are acting well within what should be expected of them by doing everything they can to defend themselves from other threats. John Locke may very well make this argument by insisting that people must necessarily have power over their own body and to protect themselves against others taking any of that from them (1980, p. 17). In Rawls’ “original position” argument, he says that the most just society is the one which would be created if people had no knowledge of their socioeconomic or other determining factors which may otherwise give them an advantage or disadvantage over others (1980, pp. 102-104). This argument may be able to be extended to apply to the discussion around CRISPR technology and artificial genetic modification: if the most just society is the one that would be created if people were unaware of their innate privileged characteristics, then CRISPR may give back some advantage to those who, through no fault of their own, were innately disadvantaged by their genetics.

However, it must be acknowledged that CRISPR currently is very expensive, experimental, and not generally covered by insurance plans (Moschos, 2018). Because of this, there are other philosophers who, while acknowledging a person’s bodily autonomy, would also disagree with the use of CRISPR until it is more widely available. Perhaps chiefly among these philosophers would be Thomas Hobbes, who believes that while there may be disparities among people, these disparities are not to be so great that a group of people would be unmanageable in their superiority over others; in fact, Hobbes goes so far as to assert that nature has ensured that any one person or group of people could not be unduly superior over another (1994, p. 74). This being the case, the argument could then be made that based on that, artificially altering one’s genetic code to give them various biological advantages against disease or even for aesthetic purposes would be impermissible. Further, the extension of the original position argument to CRISPR would lose some weight here since those who would be advantaged by genetic modification would be those who are able to access it and those with this access would most likely be the ones who need additional advantages the least.

Another consideration needs to be that of parents performing CRISPR on their children, either prior to or after birth. Since we are at a point in scientific advancement where genetic tests can be run on fetuses and young children to determine if there will be birth defects or other health issues later in life, CRISPR could be used not only to affect this but also potentially to create “designer babies” or children with certain aesthetic traits as well, such as eye and hair color (Milova, 2018). While the aforementioned Hobbesian objection to utilizing CRISPR applies in this case as well, it may be the case that children are not imbued with the same autonomy as adults are. Locke addresses this directly, saying that parents have a certain “rule and jurisdiction” over their children until they are themselves adults (1980, p. 31). So while the Hobbesian objection may stand against the utilization of CRISPR more generally, the bodily autonomy argument, per Locke, would likely not extend to children. And if we were to reach a point where CRISPR technology was reasonably accessible to everybody, the Hobbesian objection would also no longer be applicable. Thus, the biggest barrier to the philosophical or ethical considerations to the utilization of CRISPR technology is its current status as a luxury; should this status be revised through societal or scientific advancement, or both, with regards to CRISPR becoming more accessible to those with lesser means, such a philosophical barrier would no longer exist.

References

• Babačić, Haris, et al. “CRISPR-Cas Gene-Editing as Plausible Treatment of Neuromuscular and Nucleotide-Repeat-Expansion Diseases: A Systematic Review.” PLoS ONE, vol. 14, no. 2, Feb. 2019, pp. 1–32. EBSCOhost, doi:10.1371/journal.pone.0212198.
• Hobbes, T. Leviathan: with selected variants from the Latin edition of 1688; Curley, E., Ed.; Hackett Pub. Co.: Indianapolis, 1994.
• Locke, J. The Second Treatise of Government; Macpherson, C. B., Ed.; Hackett Publishing Co.: Indianapolis, 1980.
• Milova, E. Would I Want a Designer Baby? CRISPR, Gene-Editing, and You. Life Extension Advocacy Foundation [Online] November 29, 2018. https://www.leafscience.org/would-i-want-a-designer-baby/ (accessed Jun 6, 2019).
• Moschos, S. Gene Therapy is Now Available, But Could Cost Millions Over a Lifetime, Says Scientists. Independent [Online] April 2, 2018. https://www.independent.co.uk/life-style/health-and-families/gene-therapy-cost-rare-genetic-diseases-treatment-expensive-research-a8275391.html (accessed Jun 6, 2019).
• Rawls, J. A Theory of Justice: Revised Edition; The Belknap Press of Harvard University Press:Cambridge, 1999.
• Thomas, Mark, et al, “Collateral Damage and CRISPR Genome Editing.” PLoS Genetics, vol. 15, no. 3, Mar. 2019, pp. 1–8. EBSCOhost, doi:10.1371/journal.pgen.1007994.
• Vogel, Kathleen M., and Sonia Ben Ouagrham-Gormley. “Anticipating Emerging Biotechnology Threats: A Case Study of CRISPR.” Politics & the Life Sciences, vol. 37, no. 2, Fall 2018, pp. 203–219. EBSCOhost, doi:10.1017/pls.2018.21.