Genetically Modified Illnesses : Cancer

What technology is used to resolve this issue?

Then, somatic genome editing comes into place. This consists into changing a being’s deoxyribonucleic acid using CRISPR-Cas9, which is created from a naturally occurring genome editing system in bacteria. This bacteria catches pieces of DNA from entering viruses to make CRISPR-Cas9 which are smaller DNA segments that allow removing, adding, or mixing sections of the DNA sequence (Turk, J. 2020). This technology lets scientists edit disease-causing DNA within the body's non-reproductive cells, the somatic cells. This type of technology is known as gene therapy. This is used by doctors for the replacement of a faulty gene in an attempt to cure diseases or improve a body's ability to fight them. Gene therapy helps to treat many illnesses, including cancer (MayoClinic, 2017).

How is it used specifically with cancer?

When used with blood cancer, for example, it is referred to as T cell therapy. Cells are taken from a patient’s blood to be modified and re-programmed using synthetic genes that allow recognition of cancer cells. Synthetic cells then instruct the T cells to make a chimeric antigen receptor which are T cells that have been engineered to create an artificial T cell receptor for use in immunotherapy and to enforce targeting cancerous cells. Lastly, engineered lymphocytes are given back to the patient intravenously, and start working. Part of the receptor injected is based on an antibody that can identify a cancer cell, so when encountering this, the receptor activates the T cell, and instructs it to attack the cancer, replicate itself, and activate other parts of the immune response to the fight. An example of this technology in action is when it was tested at the University of Pennsylvania. Scientists first made modifications to T cells by adding a synthetic gene which gave them a receptor - a smooth and claw-like protein - that could “see” NY-ESO-1, a molecule on some cancer cells. CRISPR was then used to remove three genes: two that could interfere with the NY-ESO-1 receptor and another that limited the cells’ cancer-killing abilities. The finished NYCE T cells were multiplied in large numbers and then injected into patients (National Human Genome Research Institute, 2017).

How is the modification made to cancerous cells? 

The technology used to modify human cancerous cells - CRISPR-Cas9 - has two molecules that modify the DNA. First, the enzyme called Cas9. This is a pair of molecular scissors which go in the DNA strands to cut them at a specific location. It then leaves a spot for new strands of DNA to be added, removed, or mixed. The second method is by using a guide RNA. In theory, this guide only aims for a specific sequence and does not reach other sections of the genome. This inserted piece of pre-designed RNA sequence is part of a longer RNA scaffold. This is connected to the DNA and pushes Cas9 to the right part of the genome for the enzyme to cut at the right spot. This is when the cells realize that something is incorrect within the DNA. At this time, scientists use the DNA repair machinery to introduce necessary cells in the aimed genome (Your Genome, n.d). 

What is controversial about this change? 

Most issues with genetically modifying humans are divided between a lack of research and of specificity concerning the change. Off-target activity is a controversy, and it means that CRISPR could cut areas outside the aimed DNA gene to modify or leave an empty space, which could turn new cells into cancerous cells and cancel the effort made during the process. Another issue may be getting the CRISPR technology to be delivered into one’s cells. This is commonly done using a co-opt virus and so rather than conveying genes that cause disease, the virus is modified to carry genes for the guide RNA and Cas. Some viruses that used to carry CRISPR could also infect more than targeted areas which is why researchers have started using nanocapsules - tiny structures made to deliver CRISPR components to specific cells. Scientists also feel controversial as to how human bodies will react to this new technology - specifically, the human immune system. It is also wondered if editing cells inside the body could accidentally make changes to sperm or egg cells that are passed onto future generations. Though for all ongoing CRISPR studies, patients’ cells are removed and edited outside of their bodies since this ex vivo method is safer and offers more control (National Cancer Institute, n.d). 

What are pros of this technology? 

There are also good points concerning genetic modification in humans. To start, due to cancer, life expectancy decreases by about 11 years for each being. Being able to genetically modify people with this disease could extend the lifespan of humans in general and as genetic editing can reverse the most fundamental reasons for the body’s natural decline on a cellular level, it can improve both the span and the quality of life of people later on. Furthermore, scientists are working on making it so that the genetically modified DNA strand that is missing cancerous cells can be a hereditary trait - which would mean that future generations would have very few chances of having cancer as their genes would not represent it. Thirdly, most causes of cancer are unknown and once neoplastic change is established, there is no cure other than total surgical removal or replacement of the cancerous cell. Though chemotherapy and radiation therapy are life-prolonging treatments, they rarely totally cure cancer. This means that if this change can be done through genetic editing, it would be permanent and certitude of the disease leaving would be guaranteed. Additionally, the therapy itself is cheap to provide, and all the “money” said  to be used for it mostly goes towards new research rather than towards offering the treatment. Lastly, this genetic modification has shown high levels of success and it is explained that as humans can live without healthy B cells, diseases such as leukemia are good candidates for the therapy, and, so far, the it has had response rates as high as 70% to 90% (Harvard Health Publishing School, 2017). 

What is my opinion on them (impacts on our society)

To conclude, it is believed that genetic modification in humans for diseases is a positive aspect, that offers more justice and equality as to different beings’ health since “bad genetics” or lower life spans would end for many, improving people’s happiness, - as being cured from a disease would decrease levels of stress and of anxiety. An individual having genetically modified genes would also benefit their siblings or blood related ones who might turn out to have the same illness, and for who getting a treatment would then prove to be easier. For society, this genetic modification is easier too, as recently, methods to transfer genes without needing DNA templates, DSBs, or independence on HDR have been found. And though these are positive impacts on our society, negative ones can be found as well. The modification could represent favoritism for the wealthier, who have more access to developed technology (Frontiers in Medicine, 2021). But also the simple impact of this on future generations, as well as the complications that could come with people using the technology in their own way. Informed consent is an issue as well, and many patients may not know about secondary effects or about consequences if CRISPR Cas9’s transfer is intercepted. And finally, research could be done during the medical processes and professionals could be benefiting off of people trying to get treated. 

Blackburn, L. 2018. Somatic genome editing: An overview. Retrieved from: https://www.phgfoundation.org/briefing.

Frontiers in Medicine. 2021. CRISPR/Cas: Advances, Limitations, and Applications for Precision Cancer Research. Retrieved from: https://www.frontiersin.org/articles

Iredale, R. 2006. What choices should we be able to make about designer babies? A Citizens’ Jury of young people in South Wales. Retrieved from: https://onlinelibrary.wiley.com

Synbio Technology, Genes for Life. N.d. Genome Editing Technology vs Transgenic Technology. Retrieved from: https://www.synbio-tech.com/genome-editing-vs-transgenic/

T, Biol. 2020. Bioethical issues in genome editing by CRISPR-Cas9 technology. Retrieved from: 2020https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129066/

Your Genome. N.d. What is CRISPR-Cas9? Retrieved from: https://www.yourgenome.org/facts/what-is-crispr-cas9

MayoClinic. 2017. Gene Therapy. Retrieved from: https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384

National Cancer Institute. N.d. What Is Cancer? Retrieved from: https://www.cancer.gov/about-cancer/understand%20disease%20ca.

National Human Genome Research Institute. 2017. What are the Ethical Concerns of Genome Editing? Retrieved from: https://www.genome.gov/about-genomics

Harvard Health Publishing School. 2017. Teaching T Cells to Fight Cancer. Retrieved from: https://www.health.harvard.edu/cancer/teaching-t-cells-to-fight-cancer