The Feasibility of Spidey Senses

Figure 1: CRISPR-Cas9 system [1]

Written by Emmanuelle Bal ‘28

Edited by Andrew Ni’ 26

What if the genetic engineering spider bite inflicted on Peter Parker was just a slim stretch from reality? What if there truly was a way to use technology to change your DNA? Maybe not in a superhero transforming way, but in one that could cure diseases or even make them preventable? In 2005, Jennifer Doudna and Emmanuelle Charpentier discovered just the technology that could do it: CRISPR-Cas9. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 is a gene editing technology that allows scientists to modify an organism's DNA by altering specific parts of the genome. This new technology has excited many geneticists since it has been discovered but has also frightened many ethicists.

CRISPR-Cas9 is a gene-editing tool containing a guide RNA strand and a CRISPR associated protein (Cas) that cuts the DNA [1]. The guide RNA is able to recognize target sequences in the DNA that it wants to break. When this sequence is found, it acts as a hand, guiding the Cas9 to the particular place in the DNA strand. Then, the Cas9 binds to the DNA at a desired point and acts as scissors, causing a double-stranded break in the DNA [2].

Once it was discovered that the CRISPR-Cas9 complex could be used to create these changes in DNA, the next step was to figure out whether it could be controlled to cut specific strands of DNA. What scientists found is that they could manipulate Cas9 to not only cut parts of DNA but also activate certain gene expression. That is, the parts of the DNA that were manipulated could lead to different functions being produced in the cell and body.

We now know that CRISPR-Cas9 may lead to many fascinating scientific discoveries, ranging from genetically modifying watermelons to be more herbicide resistant [3] or modifying fetuses to possibly prevent them from having genetic diseases [4]. The rather extreme consequences of this tool, though, have led to a rise of bioethical questions. Could genetically modifying humans lead to a furthering of eugenics theory? Greater healthcare inequality? Millions of spider men roaming the streets of New York?

For these reasons, among others, in 2015, Jessica Douda organized a conference that reflected on the ethical issues related to genomic modification [5]. Many came to the conclusion that the aforementioned questions were of great importance, and so was the consideration of off-target DNA editing risks. That is, a downstream effect from CRISPR-Cas9 editing in a DNA strand. Since this conference, many publishings have come out denouncing the use of genetically modifying humans in a way that may introduce heritable changes in embryonic cells.

But of course, there are others who see the potential that CRISPR-Cas9 holds. What if we could eradicate HIV? End the presence of genetic diseases? After all, are there not risks in all medical procedures carried out? In 2018, someone believing this line of thought carried out a CRISPR-Cas9 experiment in two twins. This scientist, He Jiankui, illegally conducted an experiment to modify the genes of two girls to make them HIV immune. Using CRISPR technology, he disabled the CCR5 gene which enables HIV infection [6].

As this is the only example of fetuses being genetically engineered, it makes it a perfect example to raise the questions we pondered upon earlier. Firstly, we can start with the side effects that may evolve from this treatment. A glaring one is that the intervention with the CCR5 genes leads to a higher risk of infection from the West Nile virus and severe flu [7]. This is a perfect example, among many others, of an objective risk to gene editing. But even if there were no direct risks from this gene editing, would it truly be ethical? After all, the fetus is not consenting to this permanent change in its DNA, which will be passed down through generations. While I am sure these twins would not be opposed to having HIV-free children, they may be against the off-target effects streaming through their lineage. We can also look at the ethical issues on a macro level: should we be interfering with our DNA? What makes us human at our core? To what extent should we be able to exploit CRISPR-Cas9? Many would argue that creating this superhuman race is unethical while others would claim that modern medicine’s goal is inexplicably to battle what makes us naturally weaker. 

This debate will of course be never ending, but the science driving it will continue to evolve as more CRISPR-Cas9 techniques are explored. Just recently, on December 8, 2023, the FDA approved the first gene therapy utilizing CRISPR-Cas9 to treat patients with sickle cell disease. This therapy will be used in patients 12 and older and be entirely legal, making it very different from our HIV twin example [8]. But, it still lets us ponder on where CRISPR-Cas9 editing will take us in the future and if the guiding hand and the snipping scissors will ever lead us to seeing Peter Parkers everywhere.

References

1. Redman M, King A, Watson C, King D. What is CRISPR/Cas9? Arch Dis Child Educ Pract Ed. 2016 Aug;101(4):213–5.

2. Synthego [Internet]. [cited 2024 Oct 8]. What Is CRISPR: The Ultimate Guide To CRISPR Mechanisms, Applications, Methods & More. Available from: https://www.synthego.com/learn/crispr

3. Arora L, Narula A. Gene Editing and Crop Improvement Using CRISPR-Cas9 System. Front Plant Sci. 2017 Nov 8;8:1932.

4. Peddi NC, Marasandra Ramesh H, Gude SS, Gude SS, Vuppalapati S. Intrauterine Fetal Gene Therapy: Is That the Future and Is That Future Now? Cureus [Internet]. 2022 Feb 23 [cited 2024 Oct 8]; Available from: https://www.cureus.com/articles/87441-intrauterine-fetal-gene-therapy-is-that-the-future-and-is-that-future-now

5. Raposo VL. The First Chinese Edited Babies: A Leap of Faith in Science. JBRA Assisted Reproduction [Internet]. 2019 [cited 2024 Oct 8]; Available from: https://www.jbra.com.br/trab/pub/download_trabalho.php?fileSource=/var/www/vhosts/jbra.com.br/media/trab/arq_1660&fileName=1%20-%201471-The.pdf&id_trabalho=674

6. Gostimskaya I. CRISPR–Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing. Biochemistry Moscow. 2022 Aug;87(8):777–88.

7. Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. The Journal of Experimental Medicine. 2006 Jan 23;203(1):35–40.

8. U.S. Food and Drug Administration [Internet]. 2023. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease