Literature Review ROUGH DRAFT

This essay is one which is meant to provide information about the revolutionary technology that is CRISPR. To the average member of the public, student, teacher, or otherwise, which may or may not be you, the topic of CRISPR may be distant, unimportant and even hard to understand. However, the issue has many applications across various fields, and it is very likely to have an important role in our lives, from our medical treatment, to the food we eat. In this essay, given the complex and science-heavy nature of the topic, I have simplified some of the languages and facts, and omitted certain information which may not be essential to understanding the topic. Hopefully, in this way, the article can be more inclusive, more interesting, and more effective in convincing the average reader. In order to further improve my writing and make it more convincing to the audience, I have been motivated by several concepts. One of the most important has been exigence, the imperfection or issue to which a writer responds, as well as evidence and rhetoric. To me, these concepts are the most important in creating a convincing and interesting piece of writing. Therefore, I believe that putting emphasis on these is important, which is what I have aimed to do in writing this piece. In addition to this, I believe that this assignment has helped me develop skills in achieving the composition of “texts that integrate your stance with appropriate sources using strategies such as summary, critical analysis, interpretation, synthesis, and argumentation”, since my essay has been heavily reliant on sources and external information to establish an argument about this topic. Furthermore, this essay uses sources that generally do not have their own arguments, and merely provide information about the possible uses of CRISPR technology. As such, I have essentially been forced to create a text which integrates my own personal stance with the sources I use.

CRISPR: The Genetic Multitool

Few technologies, if any such have ever existed, have had the potential to make such significant ripples in the scientific community as CRISPR. From selective breeding, to modern genetic modification, and of course, CRISPR, genetic engineering has progressed throughout human history since at least the 12,000s BC. This was when, according to archaeological evidence, the first dogs were domesticated and were the first animals to be domesticated. Later came plants and crops in the 10,000s BC, which formed a human tradition and ability to control and manipulate (albeit indirectly until the 1970s) the genetic material of organisms. Direct human manipulation of genetic material came in 1973, when Herbert Boyer and Stanley Cohen created the first organism with genes from multiple sources (transgenic). In 1983, the first Genetically Modified Organism was released into the wild, a bacteria that protected crops from frost. This happened despite mass controversy and the public protesting and trashing the test site. First trials for genetically modified plants happened in 1986, and in 1994, the first genetically modified food, a tomato called the “Flavr Savr”, was commercially sold. In 2010, the first synthetically produced complete set of genes was introduced into an empty bacterial cell. Finally, in 2012, Jennifer Doudna and Emmanuelle Charpentier collaborated and developed the CRISPR/Cas9 system. CRISPR itself, though, was discovered at the end of a chain of events beginning in 1987, when Japanese researchers accidentally cloned part of a CRISPR sequence and a gene from E. coli. Though what it was was not yet known, the scientists noted the organisation of sequences, which was atypical. Later, further research in the Netherlands and Spain developed the knowledge of CRISPR, and eventually led to the creation of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) acronym, describing the nature of the DNA sequences it labels. CRISPR is a family of DNA sequences found in the genomes of bacteria and archaea (prokaryotes). The sequences are created from viral DNA from previous infections, which can be used to destroy DNA from future infections by the virus or a similar one, creating a sort of immunity. This is done by forming a complex with Cas9 (CRISPR-associated protein 9), which is controlled by CRISPR sequences and recognizes and cuts strands of DNA that are complementary to the virus-derived CRISPR sequences. By using a synthetic guide instead of viral DNA, this process, discovered by Doudna and Charpentier, can be used to edit genes, by cutting DNA and removing or adding genes in the genome. Naturally, the implications that come from this discovery are immense, as many of the world’s problems are sourced from and can be solved by genetics. However, the topic of CRISPR has attracted much scrutiny and uncertainty from the public and medical professionals, who are hesitant because of some of the possible uses and implications of CRISPR use, most notably in editing the human genome. On the other hand, CRISPR gene editing is not only precise, but cheap, allowing it to be a versatile method for genetic engineering with possible applications in disease prevention, food production, ecosystem and species protection and control. Because of the potential of CRISPR and its applications, it should absolutely be explored further and invested in.

Among the major possible uses for CRISPR, the first is in the area of food. Similarly to other methods of genetic engineering, CRISPR has the potential to significantly change the way in which crops and plants grow, to allow for greater availability and resilience of food. Though the benefits of genetic modification may be beneficial, we soon may not have a choice but to use them. Due to increasing consequences of global warming in the form of extreme weather and droughts as well as increasing pollution, decreasing available agricultural land, and increases in pest populations, the pressure on humanity’s food supply is increasing. One of the solutions for this may be CRISPR, which can be used to make food more resilient and resistant to the world’s changing conditions. Scientists have begun developing CRISPR technology, according to Sarah Moore at AZO Life Sciences, to create and modify crops with traits that make them more nutritious, larger, and resistant to unideal weather conditions and pests. Later, in her article to a public audience about the possible role of CRISPR in food production she says, “The potential uses of CRISPR in agriculture are vast. If the technology is successfully developed and widely adopted, there is a strong chance that it could improve food productivity and environmental stability. CRISPR technology may allow the world to produce enough crops for its growing population in adverse conditions” (Moore). Basically, according to her, the use of CRISPR to enhance the characteristics of plants could allow farmers and growers to increase and maintain their output despite weather and other negative pressures. The use of CRISPR, therefore, could be instrumental in meeting humanity’s food needs, perhaps even exceeding them, with genetically engineered crops and animals. Perhaps adding to the urgency and pressure, with the growing world population, the UN has stated that food production needs to double by 2050, which is also mentioned by Moore. Unfortunately, as Moore does say that there is increasing competition over agricultural land, space may also be an issue, and we may need to resort to genetically engineered crops to increase output without increasing or expanding the land used to farm crops. The Food and Agriculture Organization of the UN, in an informative article to public audiences on the food supply and population growth, has stated that the population of the globe will, by 2050, have grown by over two-point-three billion people, or one-third since 2009. As such, it is clear that food supplies need to be increased to feed the world population and avoid a global humanitarian catastrophe. Given the fact that CRISPR is a cheap technology to modify the genomes of organisms, this may be the perfect way to create crops that are more efficient, nutritious, and easy to farm. Should we not use CRISPR, it is hard to imagine another method in which existing issues can be solved, let alone those that are to come in the future. Reacting too late to the building crises could cause devastating disasters for humankind, triggered by a lack of food due to our exploding population and self-inflicted damage from climate change.

Another possible application of CRISPR technologies is in controlling animal populations and protecting ecosystems. In a TED Talk video on June 2nd, 2016, Jennifer Kahn, a writer for the New York Times, informing the public on the uses and applications of the CRISPR technology, described the possibilities from using CRISPR with invasive species and mosquitoes. She explains that, to possibly create a mosquito that did not transmit malaria, researchers used CRISPR to create a mosquito in which the malaria parasite could not survive, eliminating the possibility of the mosquito carrying the disease. Then, in order to get the trait to spread, CRISPR was also used to guarantee that all offspring of that modified mosquito would also inherit the anti-malarial gene. This method is known as “gene drive”. In a controlled test environment, two modified mosquitoes were placed in an environment with thirty wild ones, producing 3,800 offspring within two generations. All carried the anti-malarial gene. Based on these findings, researchers estimated that, if just one percent of the Anopheles (malaria-carrying) variety of mosquito were modified with this gene, “researchers estimate that it would spread to the entire population in a year. So in a year, you could virtually eliminate malaria” (Kahn). The implications of this eradication could be monumental. Malaria is a disease that caused 627,000 deaths in 2020, according to the WHO. Up to 1,000 children die from the disease a day, and it can cause organ failure, death, seizures, coma, and other complications. Possibilities with CRISPR and controlling populations does not end there, though. Other mosquito-carried diseases can be eradicated. Kahn mentions dengue fever, chikungunya, and yellow fever. Other disease carriers like mice can also be modified. Invasive species can also be destroyed using this method. Khan, referring to the invasive Asian carp says, “All you have to do is release a gene drive that makes the fish produce only male offspring. In a few generations, there’ll be no females left, no more carp. In theory, this means we could restore hundreds of native species that have been pushed to the brink” (Kahn). While this possibility is not without its own issues, limitations, and possible consequences, CRISPR could potentially be used to destroy invasive species that enter other ecosystems and wreak havoc, killing, eating, outpopulating, and outcompeting native species. Native habitants can therefore be rehabilitated, and our ecosystems saved, and disastrous consequences avoided. Such consequences, without intervention, could include a drastic loss in biodiversity, altering habitats, depleted food sources, and other major concerns. CRISPR can also be used to revive extinct species. By inserting the genes of an extinct species into an existing but genetically similar species, the extinct species can be revived. Wesley Dockery of Deutsche Welle, a German news agency, stated that those supporting this practice said that it could increase human understanding of “biology, evolution, and technology”, and that it would be fair and moral to restore species that died out due to “human activities”. The article by Dockery, aimed at the general public to inform on the feasible revival of extinct species like the woolly mammoth, also explores Colossal, a biotech company which is aiming to resurrect the woolly mammoth. “The resurrection of extinct species could also repair damaged ecosystems. In the case of the woolly mammoth, Colossal believes the animal could revitalise the Arctic grasslands, whose properties can mitigate global warming” (Dockery). Though this process of reviving species is reportedly very expensive, the effects it could have for various ecosystems and human science are notable. As stated in the article, extinct species could increase the biodiversity of ecosystems, interact with their ecosystems positively, and provide other benefits, especially in cases where human development has caused otherwise irreparable damage to ecosystems. Additionally, by studying extinct animals, cures to diseases could be discovered, and such revived species could be important for public perception and awareness for conservation efforts. Naturally though, the thought of “un-extincting” species has brought about uncertainty and perhaps controversy, as seen in this meme/image found on iFunny, a website for memes for the public. Seen on the right, someone has used the popular animated character Sterling Archer from Archer to joke about the possible uses of the CRISPR technology in response to news about the same company from before, Colossal, also heading efforts to revive the Tasmanian Tiger. In the meme, they compare the Tasmanian Tiger and other possible revivals to the reptilian monsters known as deathclaws from the Fallout video game franchise. While the concerns are valid, the benefits in reviving species likely outweigh the drawbacks, and referring specifically to the meme, deathclaws are obviously not real, and are not based on any creature in real life in particular. The effect of introducing such species almost certainly has a bigger effect on the ecosystems they return to than humans. Despite this opposition, serious or not, a UN report in 2019 stated that up to 1 million species are facing extinction in the near future, which is also worsened by climate change. CRISPR could be used to preserve and save such species, and maintain or even improve the environments they live in.

Lastly and perhaps most importantly, CRISPR has incredible potential in the medical field, where it could help greatly in health, disease/cancer prevention. By modifying the genes of the cells of patients or the patient themselves, various diseases and ailments can be solved. Clara Rodriguez Fernandez, in her article on LABIOTECH, informs the public on the diseases that could possibly be cured using CRISPR. According to her, scientists could cure cancer, blood disorders like sickle-cell disease, beta-thalassemia, and haemophilia, (hereditary) blindness, AIDS, cystic fibrosis, muscular dystrophy, Huntington’s disease, and COVID-19. While this is obviously not guaranteed, methods are currently being tested, and there could be related possible consequences, there are workarounds being considered. For example, in the case of Huntington’s, a neurodegenerative condition “with a strong genetic component” that is caused by “abnormal repetition of a certain DNA sequence within the Huntington gene”, CRISPR could possibly be used to treat it. However, extreme precision is required, and any errors could cause serious issues for the patient. As such, Polish researchers paired CRISPR/Cas9 with the nickase enzyme to increase gene editing precision, and researchers at the University of Illinois used a different CRISPR-associated protein to intercept mRNA responsible for the coding of mutant proteins. They are responsible for Huntington’s disease, and the use of another CRISPR-associated protein avoided the direct modification of genes, and the possible unintended consequences of doing so. More relevant to current events, CRISPR was also used for screening tests and diagnostics for COVID-19, and Fernandez says that it could be possible in the long term, to use CRISPR to directly fight viruses like COVID-19. Scientists at Stanford University were apparently using CRISPR “to cut and destroy the genetic material of the virus behind COVID-19 to stop it from infecting lung cells. This approach, termed PAC-MAN, was shown to reduce the amount of virus in solution by more than 90 percent” (Fernandez). With such positive results, the use of this technology to fight viruses could be extremely beneficial, especially considering the devastating effects such viruses like COVID-19 have had globally, with pandemics, lockdowns, and harmful economic effects. Moreover, as previously mentioned but not explained, CRISPR could also have an important role in the curing and research of cancer. A biotechnology company called CRISPR Therapeutics also announced positive results in its CRISPR allogeneic T-cell therapy trials for cancer patients, in which T cells from a donor were modified with CRISPR and administered to a patient to recognize and attack tumour cells. As explained by Hope Henderson, a writer and scientist at the Innovative Genomics Institute, in her science news article to the public on clinical trials involving CRISPR and cancer treatment, the company reported that “side effects were not severe, and the safety profile was superior to other CAR-T products. In these patients, almost 60% showed a positive response to treatment, with 21% showing no sign of disease for six months after a single treatment” (Henderson). Therefore, based on what was revealed by the company, CRISPR-related treatment was actually superior in terms of safety and similar in terms of effect to previously used and approved CAR-T therapy, where the donor of the T-cells which are being modified is the patient themselves. In addition to actually fighting cancer, CRISPR has also been used as a diagnostic tool for cancer. At Sichuan University in Chengdu, China, and the University of North Dakota in the United States, researchers Hongyi Li, Yang Yang, Weiqi Hong, Mengyuan Huang, Min Wu and Xia Zhao wrote a medical article to their peers on the uses of genome editing in therapy for diseases. In this article, they revealed that the “CRISPR-based diagnostic system referred to as SHERLOCK (specific high sensitivity enzymatic reporter UnLOCKing)… appeared to be a highly sensitive detection method when used to detect two cancer mutants, BRAF V600E and EGFR L858R”( Li, Yang, Hong, Huang, Wu & Zhao). This indicates that CRISPR, as a method of finding and cutting genes, can be used to identify genes or mutations related to the development of cancer in patients, and as a result, can be an important diagnostic tool to identify risks. The two mutations mentioned are for breast cancer and lung cancer respectively, which are major cancers among the human population. The average risk of a woman in the United States developing breast cancer is thirteen percent. Lung cancer is the second most common cancer worldwide, and one in sixteen people have a chance of developing it. As a result, lives can be saved, since the identification of risks can allow for preemptive or responsive action to be taken.

In conclusion, the applications of CRISPR are many, and show great potential for revolutionary changes in biotechnology and medicine. CRISPR has been shown to be useful in increasing productivity in food and agriculture, which with an increasing global population and intensifying consequences of global warming and climate change, is all the more urgent. CRISPR is also useful in protecting ecosystems and controlling animal populations, especially those of pests and invasive species. Invasive species and pests can do immense damage to ecosystems and native species in them, and pests can and do cause hundreds of thousands, if not millions of deaths a year. With the application of CRISPR technology, said deaths can be avoided, and our ecosystems protected. Not only that, CRISPR is also potentially capable of being used to revive extinct species, which will expand human knowledge on biology, undo extinctions induced by human factors, and may even have positive effects on ecosystems. CRISPR also has many uses in medicine. With the developments in lab-cultivation of various things, including organs, CRISPR could be used to create organs which are “hypo immunogenic”, thus eliminating the risks of organ rejection and possible related consequences. The technology is also useful for fighting against diseases, and the potential uses for the genetic modification properties of CRISPR include the viable curing of ailments like cancer, neurodegenerative diseases, viruses, and other conditions. It is with all of these uses in mind that we must make a decision on whether or not we should use CRISPR more extensively in science. Those that oppose it have valid reasons to do so, but there have been risks and implications for many steps of progress the human race has made. If we did not take steps to advance our understanding of the world and improve our lives just because there were attached risks, humanity would not be where it is. CRISPR is a valuable tool, and should be used and tested to its full extent.

Works Cited:

Dockery, Wesley. “Biotech Firm Says It Can Resurrect Extinct Woolly Mammoth – Dw – 09/14/2021.” DW.com, Deutsche Welle, 14 Sep. 2021, https://www.dw.com/en/biotech-firm-says-it-can-resurrect-extinct-woolly-mammoth/a-59171 358. Accessed 13 Mar 2023

Fernández, Clara Rodríguez. “Eight Diseases CRISPR Technology Could Cure.” Labiotech.eu, 7 Oct. 2022, https://www.labiotech.eu/best-biotech/crispr-technology-cure-disease/. Accessed 13 Mar 2023

“Global Agriculture towards 2050 – Food and Agriculture Organization.” Food and Agriculture Organization, United Nations, https://www.fao.org/fileadmin/templates/wsfs/docs/Issues_papers/HLEF2050_Global_Agricu lture.pdf?_hsenc=p2ANqtz-_tSqtRa_kWacH6zE0ow8OOwgKXW0hwgc9jzZfxZt8dTDj81f O9dIu8CGzDAiwDHkJvI3vO. Accessed 13 Mar. 2023

Henderson, Hope. “CRISPR Clinical Trials: A 2022 Update.” Innovative Genomics Institute (IGI), 18 May 2022, https://innovativegenomics.org/news/crispr-clinical-trials-2022/. Accessed 13 Mar 2023

Henderson, Sarah MooreReviewed by Emily. “Could Crispr Change the Future of Our Food?” News-Medical.net, 16 May 2022, https://www.azolifesciences.com/article/Could-CRISPR-Change-the-Future-of-our-Food.aspx #:~:text=Researchers%20have%20begun%20developing%20CRISPR,and%20with%20prefer able%20nutritional%20values. Accessed 13 Mar. 2023.

Kuscu, Cem, et al. “Applications of CRISPR Technologies in Transplantation.” American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, U.S. National Library of Medicine, Dec. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109183/. Accessed 13 Mar 2023.

Li, Hongyi, et al. “Applications of Genome Editing Technology in the Targeted Therapy of Human Diseases: Mechanisms, Advances and Prospects.” Nature News, Nature Publishing Group, 3 Jan. 2020, https://www.nature.com/articles/s41392-019-0089-y. Accessed 13 Mar 2023.

Pure_science_tech. “Inside the Plan to De- Extinct the Tasmanian Tiger CRISPR Startup Colossal Supercharges the Effort to Bring Australia’s Thylacine Back from Extinction. DO YOU WANT DEATHCLAWS? BECAUSE THIS IS HOW YOU GET DEATHCLAWS.” Ifunny.co, IFunny, 16 Aug. 2022, https://ifunny.co/picture/inside-the-plan-to-de-extinct-the-tasmanian-tiger-crispr-MOkHa0Zn 9. Accessed 20 Nov. 2022.

TEDtalksDirector, director. Gene Editing Can Now Change an Entire Species — Forever | Jennifer Kahn. YouTube, YouTube, 2 June 2016, https://www.youtube.com/watch?v=OI_OhvOumT0 Accessed 13 Mar 2023