Hello everyone, welcome back to Cellfie Magazine! Today, we are excited to share with you a thought-provoking article written by one of our excellent monthly blog writers, Eloise. This is a fascinating, and slightly controversial, topic which will likely be at the forefront of medical advancements and ethics this century. The Cellfie Team certainly learnt a lot from Eloise's research and we hope you enjoy this topical post.
Since the 1990s biologists have had a fascination with the human genome and analysing DNA sequences. From bacteria to humans, life is coded for by four bases - abbreviated to A, T, G, C - all coiled up into every plasmid or nucleus.
Being able to change a mutated/less-favourable DNA base sequence is something that was impossible a century ago, but is now coming into sight for modern technology. Prior to CRISPR gene editing, there was no efficient or tangible way to edit DNA that could be implemented into today’s medicine, farming or biological research. So, what is CRISPR?
CRISPR-Cas9 is an enzyme in bacteria and archaea that protects them from invading viruses by cutting the virus’s foreign DNA (Jinek et al., 2012). For gene editing, you can think of this enzyme as a pair of scissors that we can control and code to cut DNA in the desired places. George Church, a professor of genetics at Harvard Medical School, explained in an interview that, “Operationally, you design a stretch of 20 base pairs that match a gene you want to edit...then the [guide] RNA plus the [Cas9] protein will cut - like a pair of scissors- the DNA at that site, and ideally nowhere else.” (Vidyasagar, 2018). This newly discovered tool has catalysed a race in research to develop CRISPR technology and test the limits of its capabilities. Now you might be asking, what if it cuts the wrong place? Can you undo any edits? What effect will directly changing an organism’s DNA sequence have? Well, you’re not alone as the whole science community is trying to answer the abundance of questions CRISPR has brought about.
Medical applications of CRISPR gene editing have started to emerge, such as treating leukemia with an injection of ‘designer immune cells’ genetically engineered to combat cancer (The Guardian, 2015) or even editing human embryos to eradicate a heart disease defect (Ghose, 2017). Interestingly, humans aren’t the only organism scientists are tinkering with. ‘Gene drives’, a method of sterilising a sexually producing species through genetic editing, is gaining a lot of attention. Specifically, an “RNA-guided gene drive” that controls the spread of malaria among mosquitoes, which are the disease vector (Vidyasagar, 2018). Additionally, ‘gene drives’ are being used to reverse pesticide and herbicide resistance in species that affect the farming industry (A. Oye et al., 2014). Most research for now is kept in a laboratory, as we learn as a society where to push the boundaries and where to leave life on a natural course.
Which cells genetic engineers target is another dimension to the world of CRISPR. Germline editing targets embryos and sperm or egg cells. However, any changes made to these cells will also change the offspring of this organism for later generations. Somatic editing targets the genes of any other cells in an organism (i.e. muscle cells, red blood cells, epithelial cells, etc). This begs the question: how far do we take editing an organism’s genome? Tampering with human embryos (not just a tissue sample in a lab), for example, is attempting to produce a superior genetic profile, which offloads a whole boat of ethical concerns. This is a human life that we have the ability to recode and tweak, yet there are no set in stone consequences or policies to guide scientists of which CRISPR cut is too far (Schaefer, 2015).
After the CRISPR revelations of 2013, where CRISPR-Cas9 technology was first published to have been used to edit human cells by Church and Feng Zhang, a plethora of these ethical concerns were raised in the science community (Vidyasagar, 2018). For starters, the accuracy of these molecular scissors was largely unknown, and thus the legal limits that should be applied to CRISPR gene editing research was undefined. On one hand, the gene editing community was becoming insatiable for new possibilities, but, on the other hand, a wave of people felt that scientists were beginning to ‘play god’ by even touching DNA. People are calling for there to be policies - advised by experts in law, bioethics and, importantly, genetics - put into place to ‘consider these important issues’ (Baltimore et al., 2015).
As you’re reading this, there are many projects using CRISPR that are going ahead to find new innovative uses of the gene editor, and also to assess the ethical risks that follow. So, keep an eye out for scientific journals and papers that will, inevitably, change the face of science as we know it.
References:
A. Oye, K., Esvelt, K., Appleton, E., Catteruccia, F., Church, G., Kuiken, T., Baryam Lightfoot, S., McNamara, J., Smidler, A. and P. Collins, J., 2014. Regulating gene drives. Science, [online] (6197), pp.626-628. Available at: <https://science.sciencemag.org/content/345/6197/626.full> [Accessed 26 March 2021].
Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R., Church, G., Corn, J., Daley, G., Doudna, J., Fenner, M., Greely, H., Jinek, M., Martin, G., Penhoet, E., Puck, J., Sternberg, S., Weissman, J. and Yamamoto, K., 2015. A prudent path forward for genomic engineering and germline gene modification. Science, [online] 348(6230), pp.36-38. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394183/>.
Ghose, T., 2017. Scientists Erase Heart Disease Defect in Human Embryos. [online] livescience.com. Available at: <https://www.livescience.com/59971-crispr-used-on-embryos-in-us.html> [Accessed 26 March 2021].
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. and Charpentier, E., 2012. A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science, [online] 337(6096), pp.816-821. Available at: <https://pubmed.ncbi.nlm.nih.gov/22745249/>.
Schaefer, G., 2015. Why Treat Gene Editing Differently in Two Types of Human Cells? | SciTech Connect. [online] Scitechconnect.elsevier.com. Available at: <http://scitechconnect.elsevier.com/treat-gene-editing-differently-human-cells/> [Accessed 26 March 2021].
The Guardian, 2015. Baby girl is first in the world to be treated with 'designer immune cells'. [online] Available at: <https://www.theguardian.com/science/2015/nov/05/baby-girl-is-first-in-the-world-to-be-treated-with-designer-immune-cells> [Accessed 26 March 2021].
Vidyasagar, A., 2018. What Is CRISPR?. [online] livescience.com. Available at: <https://www.livescience.com/58790-crispr-explained.html> [Accessed 26 March 2021].