Literature Review FINAL DRAFT

CRISPR: The Genetic Multitool

There are very few technologies that have had the potential to shape the scientific community in such a significant way as CRISPR. Since at least 12,000 BC, genetic engineering has progressed through selective breeding, modern genetic modification, and of course, CRISPR. It was around this time that the first dogs were domesticated, according to archaeological evidence. Humans developed the ability to control and manipulate organism genetic material as plants and crops emerged in the 10,000s BC. Transgenic organisms were first created by Herbert Boyer and Stanley Cohen in 1973, the year in which humans manipulate genetic material directly. The first GMO, a bacteria that protected crops from frost, was released into the wild in 1983. Even though the test site was trashed and protested by the public, this took place anyway. A tomato called the “Flavr Savr ” was the first genetically modified food commercially sold in 1994 after the first phase of trials in 1986. An empty bacterial cell was introduced with the first synthetically created set of genes in 2010. The CRISPR/Cas9 system was developed in 2012 by Jennifer Doudna and Emmanuelle Charpentier. As a result of an accident in 1987, Japanese researchers were able to clone the CRISPR gene and part of two CRISPR sequences from E. coli. Although the scientists were unsure what it was, the sequences seemed to be organized differently. The CRISPR acronym, which is short for clustered regularly interspaced short palindromic repeats, was developed in the Netherlands and Spain in response to further research into CRISPR. Prokaryotes and bacteria both have DNA sequences called CRISPRs. A virus can make these sequences by destroying DNA from previous infections, preventing them from infecting the body again. The CRISPR sequences directly control Cas9 (CRISPR-associated protein 9), which recognizes complementary strands of DNA and cuts them. Cas9 is controlled by viral CRISPR sequences. It works by cutting DNA and removing or adding genes to the genome, rather than using viral DNA, as suggested by Doudna and Charpentier. As genetics can contribute to and solve a number of the world’s problems, it has tremendous implications. It is unclear, however, how CRISPR will be used or what the implications will be for the public and medical professionals. Of particular concern is the possibility of editing the human genome using CRISPR. Meanwhile, CRISPR gene editing, although precise, is also inexpensive. It is useful in preventing diseases, producing food, controlling ecosystems, and protecting species, among other things.  The potential of CRISPR makes it an investment that should be explored and further developed.

CRISPR has major possible uses in food. In a similar way to other genetic engineering methods, CRISPR can help improve the availability and resilience of food by affecting how crops grow. It is possible that genetic modification will become a necessity soon, even if the benefits are favorable. As global warming’s impacts increase in the form of extreme weather and droughts, pollution, declining agricultural lands, and pest populations, humans’ food supply is under increasing stress. CRISPR may offer a solution to this problem since it can be used to make food more resilient and resistant to climate change. Scientists have begun developing CRISPR technology, according to Sarah Moore at AZO Life Sciences. This is 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 of improving food productivity and environmental stability. CRISPR technology may allow the world to produce enough crops for its growing population under adverse conditions” (Moore). Her main argument was that CRISPR could increase and maintain farmers’ and growers’ output no matter what the weather or other pressures are. In addition to meeting our food needs, CRISPR can assist humans in exceeding them by genetically engineering crops and animals. Because of the growing population of the world, Moore estimates that food production will be doubled by 2050. Also, GE crops may increase production without increasing farmland and may solve the problem of space due to increasing competition for agricultural land. The UN food and Agriculture Organization says the world population will have grown by one-third since 2009, or more than two-point-three billion people, by 2050, in an article on food supply and population growth. In order to feed the world population and prevent a global humanitarian catastrophe, it is obvious that food supplies need to be increased. It is possible to create more efficient, nutritious, and easy-to-farm crops using CRISPR since it is a cheap technology for editing DNA. It would be difficult to imagine a better way to solve today’s problems, let alone the ones that will arise in the future, should we not use CRISPR. A lack of food triggered by our exploding population and self-inflicted damages caused by climate change could cause devastating disasters for humankind if we react too late to building crises.

Controlling animal populations and protecting ecosystems are other possible applications of CRISPR technologies. An article in the New York Times on June 2nd, 2016, explained how CRISPR can be used against mosquitoes and invasive species TED Talk video. CRISPR was used to create a mosquito that was incapable of carrying malaria parasiteControlling animal populations and protecting ecosystems are other possible applications of CRISPR technologies. An article in the New York Times on June 2nd, 2016, explained how CRISPR can be used against mosquitoes and invasive species in TED Talk video. CRISPR was used to create a mosquito that was incapable of carrying the malaria parasite, thereby ensuring it could not transmit malaria. Additionally, CRISPR was used as a way to guarantee that the anti-malaria gene would be passed down to the offspring of the modified mosquito. The “gene drive” method is used in this manner. Over the course of two generations of a controlled test environment, two modified mosquitoes produced 3,800 offspring with the help of thirty wild mosquitoes. 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. According to the World Health Organization, malaria caused 627,000 deaths in 2020. In addition to causing organ failure, death, seizures, coma and other serious complications, the disease kills up to 1,000 children every day. However, CRISPR has other possibilities when it comes to controlling populations. It is also possible to eradicate other diseases transmitted by mosquitoes. A number of diseases are mentioned by Kahn, including dengue fever, chikungunya, and yellow fever. Modifications can also be made to other disease carriers, such as mice. Using this method, it is also possible to destroy invasive species. 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). The use of CRISPR could potentially eradicate invasive species that provide havoc to other ecosystems, eating, out populating, and outcompeting native species, while still having its own issues, limitations, and possible consequences. Our ecosystems can be saved, and disastrous consequences can be avoided, by restoring native habitats. Depleted food sources, habitat destruction, and biodiversity loss could all occur without intervention. CRISPR can also be used to revive extinct species. Depending on genetic similarities, it might be possible to revive an extinct species by combining its genes with those of a genetically similar existing species. The German news agency Deutsche Welle quoted Wesley Dockery as saying that those who supported this practice said it could enhance human understanding of “biology, evolution, and technology” and that it would be fair and moral to restore species that have disappeared because of “human activity”. A biotech company called Colossal aims to revive the woolly mammoth in the article by Dockery, aimed at informing the public on the possibility of reviving extinct species like 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). The consequences could be significant for various ecosystems and human science, even though this process of reviving species is reportedly very expensive. Extinct species could provide benefits for ecosystems, such as greater biodiversity, improved interaction with ecosystems, and restoring ecosystems that have been damaged by human activity. In addition to discovering cures for diseases by studying extinct animals, the revival of such a species could increase public awareness of conservation efforts. It is almost certain that the introduction of such species will negatively affect the ecosystems that they return to. Climate change also worsens the threat of extinction for 1 million species in the near future, despite this opposition, however serious. As well as maintaining or even improving the environment in which these species live, CRISPR could be used to preserve and save such species., thereby ensuring it could not transmit malaria. Additionally, CRISPR was used as a way to guarantee that the anti-malaria gene would be passed down to the offspring of the modified mosquito. The “gene drive” method is used in this manner. Over the course of two generations of a controlled test environment, two modified mosquitoes produced 3,800 offspring with the help of thirty wild mosquitoes. 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. According to the World Health Organization, malaria caused 627,000 deaths in 2020. In addition to causing organ failure, death, seizures, coma, and other serious complications, the disease kills up to 1,000 children every day. However, CRISPR has other possibilities when it comes to controlling populations. It is also possible to eradicate other diseases transmitted by mosquitoes. A number of diseases are mentioned by Kahn, including dengue fever, chikungunya, and yellow fever. Modifications can also be made to other disease carriers, such as mice. Using this method, it is also possible to destroy invasive species. 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). The use of CRISPR could potentially eradicate invasive species that provide havoc to other ecosystems, eating, out-populating, and outcompeting native species, while still having its own issues, limitations, and possible consequences. Our ecosystems can be saved, and disastrous consequences can be avoided, by restoring native habitats. Depleted food sources, habitat destruction, and biodiversity loss could all occur without intervention. CRISPR can also be used to revive extinct species. Depending on genetic similarities, it might be possible to revive an extinct species by combining its genes with those of a genetically similar existing species. The German news agency Deutsche Welle quoted Wesley Dockery as saying that those who supported this practice said it could enhance human understanding of “biology, evolution, and technology” and that it would be fair and moral to restore species that have disappeared because of “human activity”. A biotech company called Colossal aims to revive the woolly mammoth in the article by Dockery, aimed at informing the public on the possibility of reviving extinct species like 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 revitalize the Arctic grasslands, whose properties can mitigate global warming” (Dockery). The consequences could be significant for various ecosystems and human science, even though this process of reviving species is reportedly very expensive. Extinct species could provide benefits for ecosystems, such as greater biodiversity, improved interaction with ecosystems, and restoring ecosystems that have been damaged by human activity. In addition to discovering cures for diseases by studying extinct animals, the revival of such a species could increase public awareness of conservation efforts. It is almost certain that the introduction of such species will negatively affect the ecosystems that they return to. Climate change also worsens the threat of extinction for 1 million species in the near future, despite this opposition, however serious. As well as maintaining or even improving the environment in which these species live, CRISPR could be used to preserve and save such species.

Last and most importantly, CRISPR holds so much promise for health and cancer prevention in the medical field. A variety of diseases and ailments can be solved by modifying the genes of patients’ cells or themselves. CRISPR is one of the potential cures Clara Rodriguez Fernandez mentions in her article for LABIOTECH. In her view, scientists can cure cancer, AIDS, cystic fibrosis, muscular dystrophy, Huntington’s disease, and COVID-19 as well as blood disorders such as sickle-cell disease, beta-thalassemia, and hemophilia. It is obvious that this is not guaranteed, but methods are currently being tested, and workarounds have been considered in case there are any other related consequences. CRISPR may be able to treat Huntington’s disease, for instance, a neurodegenerative disorder characterized by “abnormal repetition of a certain DNA sequence within the Huntington gene”. Patient safety is paramount, so any mistake could lead to serious consequences. To increase gene editing precision, Polish researchers combined CRISPR/Cas9 with the nickase enzyme, while a different CRISPR-associated protein was used by researchers at the University of Illinois to intercept mutant protein mRNAs. Huntington’s disease is caused by them, and a different CRISPR-associated protein was used to avoid the possibility of direct gene modification and possible unintended consequences. Fernandez says that in the long term, CRISPR may be able to fight viruses like COVID-19 directly using CRISPR, which is more relevant to current events. 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). These positive results indicate that this technology could be extremely beneficial in fighting viruses, especially when we consider the devastating effects COVID-19 has had worldwide, such as pandemics, lockdowns, and economic effects. In addition, CRISPR could have a significant impact on cancer research and curing, as previously noted but not explained. As part of its CRISPR allogeneic T-cell therapy trials, biotechnology company CRISPR Therapeutics reported positive results in the identification and destruction of tumor cells by T cells from a donor. In her science news article explaining the clinical trials involving CRISPR and cancer treatment, Hope Henderson, a writer, and scientist at the Innovative Genomics Institute, explained to the public that the company reported no severe side effects and a superior safety profile compared to other CAR-T treatments. 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). As a result, based on what the company revealed, CRISPR-related treatments actually outperform CAR-T therapies in terms of safety and effectiveness, since the cells being altered belong to the patient. Cancer diagnostics have been made possible by CRISPR in addition to making cancer treatment more effective. An article on how genome editing can be used in therapy for diseases was written by Hongyi Li, Yang Yang, Weiqi Hong, Mengyuan Huang, Min Wu, and Xia Zhao at Sichuan University in Chengdu, China, and the University of North Dakota in the United States. 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). Thus, with CRISPR as a method of identifying and cutting genes, one of the most important diagnostic tools to identify cancer risks is the ability to identify genes or mutations related to cancer in patients. Cancers that are commonly found among the human population are breast cancer and lung cancer. Breast cancer is the second leading cause of death among women in the United States. One in sixteen people have a chance of developing lung cancer, which is the second most common cancer worldwide. Thus, identifying risks may lead to the prevention or reduction of lives, because the action can be taken preemptively or in response.

In conclusion, CRISPR has the potential to revolutionize biotechnology and medicine with its many applications. As the world population grows and global warming and climate change intensify, it becomes even more urgent to use CRISPR in food and agriculture to increase productivity. In addition to protecting ecosystems, CRISPR also helps control invasive species and pest populations. Pests can and do kill hundreds of thousands of animals every year, and invasive species can do extensive damage to ecosystems and native species. We can protect our ecosystems and avoid such deaths by applying CRISPR technology. Additionally, CRISPR could also be used to revive extinct species, thus expanding human knowledge of biology, undoing the consequences of human-induced extinctions, and even benefiting ecosystems. CRISPR also has many uses in medicine. It is possible to use CRISPR to create organs that are “hypo immunogenic” with the development of lab cultivation of various things, including organs. This would eliminate the risk of organ rejection and possible consequences resulting from rejection. The genetic modification properties of CRISPR technology could also be applied to alleviate cancer, neurodegenerative diseases, viruses, and other ailments. CRISPR should be used more extensively in science with all of these uses in mind. The opposition to it has valid reasons, but the human race has made many steps forward with risks and implications. A world in which the advancement of our understanding of the world and the improvement of our lives would not be possible without taking steps to advance them. Using CRISPR to its fullest extent is crucial, and its effectiveness should be tested.

 

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-59171358. Accessed 23 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 23 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_Agriculture.pdf?_hsenc=p2ANqtz-_tSqtRa_kWacH6zE0ow8OOwgKXW0hwgc9jzZfxZt8dTDj81fO9dIu8CGzDAiwDHkJvI3vO. Accessed 23 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 23 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%20preferable%20nutritional%20values.  Accessed 23 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 22 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

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 23 Mar 2023