CRISPR: Genetic Scissors, Scientists are Editing Genes?

When gene editing comes up, most people probably think about Marvel super soldiers like Captain America or the way that Jurassic Park brought back dinosaurs. Although these are some theoretical applications of gene editing and quite outlandish compared to what gene editing actually can do, they reflect the general public’s perception of this technology as a powerful paradigm-shifting one. The ability to artificially modify the DNA of living beings has massive implications, which is why scientists are having many intense conversations about when, where, and if we should use it. Join me in an exploration of the current state of gene editing technology and the ethical conversation surrounding its use.

The CRISPR-Cas9 complex is one of the most used tools for gene editing because of its unprecedented precision and its ability to snip specific portions of DNA out of an organism’s genetic code. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas9 is the protein that does the snipping. The CRISPR-Cas9 system was originally identified as an adaptive immunity mechanism for bacteria. What this means is that CRISPR, more specifically, is the region of the bacterial genome that stores fragments of viral DNA that have been encountered by the bacterium before. The Cas9 component then uses copies of viral DNA found in the CRISPR arrays as a molecular mugshot to identify matching viral DNA that is harmful to the bacteria, in which case it is cut out the bacterial DNA by the Cas9 protein to neutralize the threat.

Years after its discovery in 1987, scientists made the discoveries necessary to realize how to re-engineer the protein complex to be a programmable and precise gene editing tool. Using the CRISPR-Cas9 complex’s ability to identify specific parts of an organism’s DNA and snip it out, as well as attempting to harness the DNA double-strand break (DSB) repair pathway to the best of our ability, scientists found that this technology has the potential to revolutionize gene therapies. CRISPR, in our current understanding of it, and the cellular mechanisms surrounding its effective use, can cleave DNA at specific sites dictated by scientists, in which foreign DNA can then be inserted.

Scientists today are focused on using CRISPR to modify specific genetic code to eliminate genetic diseases. In other words: Predisposed to a disease? Snip it out! CRISPR is also used in agriculture to alter the genes of crops to make them exhibit more useful traits, like being more resistant to harsh conditions. One can imagine the possibilities that gene editing tools such as this can offer, but it is important to realize where we are and what we can actually do as of now. Scientists’ ability to use CRISPR-Cas complexes and harness the cellular and molecular pathways that are involved in DNA repair is still quite limited. It is possible to use CRISPR to correct genetic mutations and regulate gene expression, but scientists have only been able to tackle diseases like sickle cell that we know a lot about and are caused by only a single genetic mutation. Furthermore, CRISPR is still prone to off-target effects that could alter the genetic code somewhere that wasn’t intended, causing serious downstream damage that could even be fatal. Due to the sensitive nature of DNA, adverse effects from even one ill-placed edit could be devastating and permanent. This is why it is imperative to recognize that scientists very carefully teeter between the extremes of both the benefits this technology offers and the risks to any individual patient before actually applying it.

With all the amazing capabilities I’ve discussed so far, it is easy to run wild with the possibilities of how this technology can be implemented into society. Often, particularly in online spaces, people discuss how, with gene editing technology, designer babies are inevitable, and one day, gene editing technology will be applied to control aspects like beauty or intelligence. This is a scary thought that many people have, especially when it comes to the modification of embryos, but I think it’s important to understand that these ideas presume a level of genetic determinism that science simply does not support. Despite this, it doesn’t mean that there isn’t anything to be wary of.

One of the most important considerations that we must acknowledge is that with the disparities that already exist in access to specialty healthcare or the historical exclusion of marginalized identities as candidates for experimental medicine, gene editing has great potential to entrench social inequalities. Gene therapies have risen to be one of the most expensive kinds of treatment a patient can get. In ICER’s May 2021 issue of JCMP, 2 gene therapy treatments that manage hemophilia A could incur a lifetime cost of $15-$18 million. The inequitable access to expensive gene therapies has the potential to create an even greater divide between socioeconomic classes that have historically had and have not had access to life-saving treatment. This is especially pertinent in the field as gene editing is a light of hope for some of the most grim of diagnoses, such as Huntington’s disease or other rare genetic disorders with few treatment options. 

As we continue to watch this technology develop, it is important that the conversation surrounding gene editing technology is an informed one. CRISPR-Cas9 is not the all-powerful, society-changing technology that science fiction has led us to imagine, but it also isn’t something to dismiss as dangerous and dystopian. Be sure to stay posted with C2ST and other science communication pages to stay informed on this and other developing technologies.